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2.
Fertil Steril ; 111(5): 842-850, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31029238

RESUMO

Male infertility is a heterogenous disease process requiring the proper functioning and interaction of thousands of genes. Given the number of genes involved, it is thought that genetic causes contribute to most cases of infertility. Identifying these causes, however, is challenging. Infertility is associated with negative health outcomes, such as cancer, highlighting the need to further understand the genetic underpinnings of this condition. This paper describes the genetic and genomic tests currently available to identify the etiology of male infertility and then will discuss emerging technologies that may facilitate diagnosis and treatment of in the future.


Assuntos
Testes Genéticos/métodos , Infertilidade Masculina/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Deleção Cromossômica , Cromossomos Humanos Y/genética , Testes Genéticos/tendências , Humanos , Infertilidade Masculina/diagnóstico , Cariotipagem/métodos , Cariotipagem/tendências , Masculino , Análise Serial de Proteínas/métodos , Análise Serial de Proteínas/tendências , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico
3.
Yi Chuan ; 41(3): 243-253, 2019 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-30872260

RESUMO

Y chromosomal short tandem repeat (Y-STR) typing is the most commonly used genetic technique in forensic studies. However, there may be a limit to the application of Y-STR in forensic science as Y-STR loci are subject to loss or variation caused by the higher chromosomal structures' spontaneous mutation rate. Located in the long arm of the Y chromosome, azoospermia factor (AZF) have been shown to participate in spermatogenesis and its deletion could cause infertility. However, little is known about the Y-STR dropout pattern in individuals with Y chromosome microdeletions. In this study, 85 infertile males with Y chromosome interstitial deletion were identified and special Y-STR allele dropout patterns were analyzed by employing a Y-STR Commercial Kit and a Y chromosome Deletion Kit. Results demonstrate that AZF a region deletion are related to DYS439-DYS389I-DYS389II alleles dropout, while AZF b region or c region deletions correlate to DYS448 allele dropout. Null DYS385-DYS392-DYS448 alleles were observed in AZF b+c+d region deletion individuals. While null DYS390-Y-GATA-H4-DYS385-DYS392-DYS448 alleles were observed in AZF a+b+c+d large region deletion individuals. Our data suggest that Y chromosome microdeletions may indicate specific Y-STR locus dropout patterns.


Assuntos
Alelos , Infertilidade Masculina/genética , Repetições de Microssatélites , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Deleção Cromossômica , Cromossomos Humanos Y/genética , Haplótipos , Humanos , Masculino , Taxa de Mutação , Aberrações dos Cromossomos Sexuais
4.
Orphanet J Rare Dis ; 14(1): 16, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30642344

RESUMO

BACKGROUND: Knowledge on the prevalence of sex chromosome abnormalities (SCAs) is limited, and delayed diagnosis or non-diagnosis of SCAs are a continuous concern. We aimed to investigate change over time in incidence, prevalence and age at diagnosis among Turner syndrome (TS), Klinefelter syndrome (KS), Triple X syndrome (Triple X) and Double Y syndrome (Double Y). METHODS: This study is a nationwide cohort study in a public health care system. The Danish Cytogenetic Central Registry (DCCR) holds information on all karyotypes performed in Denmark since 1961. We identified all individuals in the DCCR with a relevant SCA during 1961-2014; TS: n = 1156; KS: n = 1235; Triple X: n = 197; and Double Y: n = 287. From Statistics Denmark, which holds an extensive collection of data on the Danish population, complete data concerning dates of death and migrations in and out of Denmark were retrieved for all individuals. RESULTS: The prevalence among newborns was as follows: TS: 59 per 100,000 females; KS: 57 per 100,000 males; Triple X: 11 per 100,000 females; and Double Y: 18 per 100,000 males. Compared with the expected number among newborns, all TS, 38% of KS, 13% of Triple X, and 18% of Double Y did eventually receive a diagnosis. The incidence of TS with other karyotypes than 45,X (P < 0.0001), KS (P = 0.02), and Double Y (P = 0.03) increased during the study period whereas the incidence of 45,X TS decreased (P = 0.0006). The incidence of Triple X was stable (P = 0.22). CONCLUSIONS: The prevalence of TS is higher than previously identified, and the karyotypic composition of the TS population is changing. Non-diagnosis is extensive among KS, Triple X and Double Y, whereas all TS seem to become diagnosed. The diagnostic activity has increased among TS with other karyotypes than 45,X as well as among KS and Double Y.


Assuntos
Síndrome de Turner/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Cromossomos Humanos X/genética , Estudos de Coortes , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Cariotipagem , Síndrome de Klinefelter/genética , Masculino , Pessoa de Meia-Idade , Aberrações dos Cromossomos Sexuais , Transtornos dos Cromossomos Sexuais/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Trissomia/genética , Cariótipo XYY/genética , Adulto Jovem
5.
Expert Rev Mol Diagn ; 19(2): 189-196, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30582381

RESUMO

OBJECTIVES: This study was aimed to report the clinical characteristics of fetal chromosomal aneuploidy diseases using noninvasive prenatal testing (NIPT) in twin pregnancies and analyze the results in terms of chorionicity, conception, and fetal fraction. METHODS: A total of 1160 women with twin pregnancies were recruited from 1 October 2015, to 1 August 2017. Next-generation sequencing technology was used to detect fetal aneuploidies, such as trisomy 21, trisomy 18, trisomy 13 and trisomy X. RESULTS: Aneuploidy was detected using NIPT in 26 fetuses, among which 18 fetal aneuploidies occurred in only one fetus of the twins. The rate of aneuploidy was 1.3% for dichorionic diamniotic twins and 0.5% for monochorionic diamniotic twins, respectively. The rate of aneuploidy was 1.2% for spontaneous pregnancy group and 1.1% for assisted reproductive technologies group. CONCLUSION: In this study, detection of trisomy 21, trisomy 18, trisomy 13, and X abnormality in twin pregnancies was confirmed to be accurate. The aneuploidies mostly occurred in only one fetus of the twins, and trisomy 21 was the most common type. The prenatal diagnostic standard for NIPT in singleton pregnancies could perform well in twin pregnancies, which means NIPT can be popularized as routine prenatal screening in twin pregnancies.


Assuntos
Síndrome de Down , Doenças Fetais , Gravidez de Gêmeos , Diagnóstico Pré-Natal , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual , Síndrome da Trissomia do Cromossomo 13 , Síndrome da Trissomía do Cromossomo 18 , Trissomia , Cromossomos Humanos X/genética , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/genética , Testes Genéticos , Humanos , Gravidez , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Trissomia/diagnóstico , Trissomia/genética , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomia do Cromossomo 13/genética , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/genética
6.
Neuropsychopharmacology ; 44(1): 9-21, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30127341

RESUMO

The study of sexual dimorphism in psychiatric and neurodevelopmental disorders is challenging due to the complex interplay of diverse biological, psychological, and social factors. Males are more susceptible to neurodevelopmental disorders including intellectual disability, autism spectrum disorder, and attention-deficit activity disorder. Conversely, after puberty, females are more prone to major depressive disorder and anxiety disorders compared to males. One major biological factor contributing to sex differences is the sex chromosomes. First, the X and Y chromosomes have unique and specific genetic effects as well as downstream gonadal effects. Second, males have one X chromosome and one Y chromosome, while females have two X chromosomes. Thus, sex chromosome constitution also differs between the sexes. Due to this complexity, determining genetic and downstream biological influences on sexual dimorphism in humans is challenging. Sex chromosome aneuploidies, such as Turner syndrome (X0) and Klinefelter syndrome (XXY), are common genetic conditions in humans. The study of individuals with sex chromosome aneuploidies provides a promising framework for studying sexual dimorphism in neurodevelopmental and psychiatric disorders. Here we will review and contrast four syndromes caused by variation in the number of sex chromosomes: Turner syndrome, Klinefelter syndrome, XYY syndrome, and XXX syndrome. Overall we describe an increased rate of attention-deficit hyperactivity disorder and autism spectrum disorder, along with the increased rates of major depressive disorder and anxiety disorders in one or more of these conditions. In addition to contributing unique insights about sexual dimorphism in neuropsychiatric disorders, awareness of the increased risk of neurodevelopmental and psychiatric disorders in sex chromosome aneuploidies can inform appropriate management of these common genetic disorders.


Assuntos
Síndrome de Klinefelter/genética , Transtornos Mentais/genética , Caracteres Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Transtornos dos Cromossomos Sexuais/genética , Cromossomos Sexuais , Trissomia/genética , Síndrome de Turner/genética , Cariótipo XYY/genética , Cromossomos Humanos X/genética , Feminino , Humanos , Síndrome de Klinefelter/psicologia , Masculino , Transtornos Mentais/psicologia , Aberrações dos Cromossomos Sexuais , Transtornos dos Cromossomos Sexuais/psicologia , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/psicologia , Síndrome de Turner/psicologia , Cariótipo XYY/psicologia
7.
Horm Res Paediatr ; 89(3): 205-210, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29566378

RESUMO

BACKGROUND/AIMS: Cholesterol side-chain cleavage enzyme (P450scc) deficiency is a rare genetic disorder causing primary adrenal insufficiency with or without a 46,XY disorder of sexual development (DSD). Herein, we report a case of the combination of primary adrenal insufficiency, a DSD (testes with female external genitalia in a setting of a 47,XXY karyotype), and Angelman syndrome. METHODS: Comprehensive genetic analyses were performed, including a single nucleotide polymorphism microarray and whole-exome sequencing. In vitro studies were performed to evaluate the pathogenicity of the novel mutation that was identified by whole-exome sequencing. RESULTS: The patient was found to have segmental uniparental disomy (UPD) of chromosome 15 explaining her diagnosis of Angelman syndrome. Whole-exome sequencing further revealed a novel homozygous intronic variant in CYP11A1, the gene encoding P450scc, found within the region of UPD. In vitro studies confirmed that this variant led to decreased efficiency of CYP11A1 splicing. CONCLUSION: We report the first case of the combination of 2 rare genetic disorders, Angelman syndrome, and P450scc deficiency. After 20 years of diagnostic efforts, significant advances in genetic diagnostic technology allowed us to determine that these 2 disorders originate from a unified genetic etiology, segmental UPD unmasking a novel recessive mutation in CYP11A1.


Assuntos
Insuficiência Adrenal/congênito , Síndrome de Angelman/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Dissomia Uniparental , Insuficiência Adrenal/genética , Feminino , Humanos , Lactente
8.
J Int Med Res ; 46(1): 107-114, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28730893

RESUMO

Objective * Chong Xie, Xiangfeng Chen, and Yulin Liu contributed equally to this work. Genetic defects are identified in nearly 20% of infertile males. Determining the frequency and types of major genetic abnormalities in severe male infertility helps inform appropriate genetic counseling before assisted reproductive techniques. Methods Cytogenetic results of 912 patients with non-obstructive azoospermia (NOA) and severe oligozoospermia (SOS) in Eastern China were reviewed in this multicenter study from January 2011 to December 2015. Controls were 215 normozoospermic men with offspring. Results Among all patients, 22.6% (206/912) had genetic abnormalities, including 27.3% (146/534) of NOA patients and 15.9% (60/378) of SOS patients. Chromosomal abnormalities (all autosomal) were detected in only 1.9% (4 /215) of controls. In NOA patients, sex chromosomal abnormalities were identified in 25.8% (138/534), of which 8% (43/534) had a 47,XXY karyotype or its mosaic; higher than the SOS group prevalence (1.1%; 4/378). The incidence of Y chromosome microdeletions was lower in the SOS group (13.2%; 50/378) than in the NOA group (17.8%; 95/534). Conclusions The high prevalence of genetic abnormalities in our study indicates the importance of routine genetic testing in severe male infertility diagnosis. This may help determine the choice of assisted reproductive technique and allow specific pre-implantation genetic testing to minimize the risk of transmitting genetic defects.


Assuntos
Azoospermia/diagnóstico , Aberrações Cromossômicas/estatística & dados numéricos , Testes Genéticos/estatística & dados numéricos , Infertilidade Masculina/diagnóstico , Oligospermia/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Adulto , Azoospermia/genética , Azoospermia/fisiopatologia , China , Deleção Cromossômica , Cromossomos Humanos Y/genética , Humanos , Infertilidade Masculina/genética , Infertilidade Masculina/fisiopatologia , Cariotipagem , Masculino , Pessoa de Meia-Idade , Oligospermia/genética , Oligospermia/fisiopatologia , Técnicas de Reprodução Assistida , Índice de Gravidade de Doença , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/fisiopatologia
9.
Hormones (Athens) ; 16(3): 318-321, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29278519

RESUMO

This case report describes a 47,XXX girl who presented very early, at the age of 14 months, with signs of sexual precocity (breast and pubic hair development, menarche) and was finally diagnosed with GnRH dependent precocious puberty with no evidence of underlying central nervous system pathology. Molecular testing did not identify any genetic defect in any of the genes tested (KISS1, KISS1R, DLK1 and the intronless MKRN3). Though previous studies have shown a link between karyotype 47,XXX and precocious puberty, this is the youngest patient reported so far. Treatment with GnRH analog was commenced and proved to be effective, indicating a successful suppression of the hypothalamic-pituitary-ovarian axis.


Assuntos
Hormônio Liberador de Gonadotropina/análogos & derivados , Puberdade Precoce/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Trissomia/genética , Pré-Escolar , Cromossomos Humanos X/genética , Feminino , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Lactente , Cariotipagem , Puberdade Precoce/tratamento farmacológico , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/tratamento farmacológico , Resultado do Tratamento
10.
Am J Obstet Gynecol ; 217(6): 691.e1-691.e6, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29032050

RESUMO

BACKGROUND: Since its debut in 2011, cell-free fetal DNA screening has undergone rapid expansion with respect to both utilization and coverage. However, conclusive data regarding the clinical validity and utility of this screening tool, both for the originally included common autosomal and sex-chromosomal aneuploidies as well as the more recently added chromosomal microdeletion syndromes, have lagged behind. Thus, there is a continued need to educate clinicians and patients about the current benefits and limitations of this screening tool to inform pre- and posttest counseling, pre/perinatal decision making, and medical risk assessment/management. OBJECTIVE: The objective of this study was to determine the positive predictive value and false-positive rates for different chromosomal abnormalities identified by cell-free fetal DNA screening using a large data set of diagnostic testing results on invasive samples submitted to the laboratory for confirmatory studies. STUDY DESIGN: We tested 712 patient samples sent to our laboratory to confirm a cell-free fetal DNA screening result, indicating high risk for a chromosome abnormality. We compiled data from all cases in which the indication for confirmatory testing was a positive cell-free fetal DNA screen, including the common trisomies, sex chromosomal aneuploidies, microdeletion syndromes, and other large genome-wide copy number abnormalities. Testing modalities included fluorescence in situ hybridization, G-banded karyotype, and/or chromosomal microarray analysis performed on chorionic villus samples, amniotic fluid, or postnatally obtained blood samples. Positive predictive values and false-positive rates were calculated from tabulated data. RESULTS: The positive predictive values for trisomy 13, 18, and 21 were consistent with previous reports at 45%, 76%, and 84%, respectively. For the microdeletion syndrome regions, positive predictive values ranged from 0% for detection of Cri-du-Chat syndrome and Prader-Willi/Angelman syndrome to 14% for 1p36 deletion syndrome and 21% for 22q11.2 deletion syndrome. Detection of sex chromosomal aneuploidies had positive predictive values of 26% for monosomy X, 50% for 47,XXX, and 86% for 47,XXY. CONCLUSION: The positive predictive values for detection of common autosomal and sex chromosomal aneuploidies by cell-free fetal DNA screening were comparable with other studies. Identification of microdeletions was associated with lower positive predictive values and higher false-positive rates, likely because of the low prevalence of the individual targeted microdeletion syndromes in the general population. Although the obtained positive predictive values compare favorably with those seen in traditional screening approaches for common aneuploidies, they highlight the importance of educating clinicians and patients on the limitations of cell-free fetal DNA screening tests. Improvement of the cell-free fetal DNA screening technology and continued monitoring of its performance after introduction into clinical practice will be important to fully establish its clinical utility. Nonetheless, our data provide valuable information that may aid result interpretation, patient counseling, and clinical decision making/management.


Assuntos
Ácidos Nucleicos Livres/sangue , Transtornos Cromossômicos/sangue , Amniocentese , Síndrome de Angelman/sangue , Síndrome de Angelman/diagnóstico , Síndrome de Angelman/genética , Amostra da Vilosidade Coriônica , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos X/genética , Síndrome do Miado do Gato/sangue , Síndrome do Miado do Gato/diagnóstico , Síndrome do Miado do Gato/genética , Síndrome de Down/sangue , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Síndrome de Klinefelter/sangue , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Análise em Microsséries , Síndrome de Prader-Willi/sangue , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Valor Preditivo dos Testes , Gravidez , Diagnóstico Pré-Natal , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/sangue , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Trissomia/diagnóstico , Trissomia/genética , Síndrome da Trissomia do Cromossomo 13/sangue , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomia do Cromossomo 13/genética , Síndrome da Trissomía do Cromossomo 18/sangue , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/genética , Síndrome de Turner/sangue , Síndrome de Turner/diagnóstico , Síndrome de Turner/genética
11.
Arthritis Rheumatol ; 69(11): 2187-2192, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28692793

RESUMO

OBJECTIVE: Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) are related by clinical and serologic manifestations as well as genetic risks. Both diseases are more commonly found in women than in men, at a ratio of ~10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease, suggesting a dose effect on the X chromosome. METHODS: We examined cohorts of SS and SLE patients by constructing intensity plots of X chromosome single-nucleotide polymorphism alleles, along with determining the karyotype of selected patients. RESULTS: Among ~2,500 women with SLE, we found 3 patients with a triple mosaic, consisting of 45,X/46,XX/47,XXX. Among ~2,100 women with SS, 1 patient had 45,X/46,XX/47,XXX, with a triplication of the distal p arm of the X chromosome in the 47,XXX cells. Neither the triple mosaic nor the partial triplication was found among the controls. In another SS cohort, we found a mother/daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in ~1 in 25,000-50,000 live female births, while partial triplications are even rarer. CONCLUSION: Very rare X chromosome abnormalities are present among patients with either SS or SLE and may inform the location of a gene(s) that mediates an X dose effect, as well as critical cell types in which such an effect is operative.


Assuntos
Cromossomos Humanos X/genética , Lúpus Eritematoso Sistêmico/genética , Mosaicismo/estatística & dados numéricos , Aberrações dos Cromossomos Sexuais/estatística & dados numéricos , Síndrome de Sjogren/genética , Alelos , Teorema de Bayes , Feminino , Dosagem de Genes , Humanos , Cariótipo , Lúpus Eritematoso Sistêmico/epidemiologia , Polimorfismo de Nucleotídeo Único , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/epidemiologia , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Síndrome de Sjogren/epidemiologia , Trissomia/genética , Síndrome de Turner/epidemiologia , Síndrome de Turner/genética
12.
Leg Med (Tokyo) ; 27: 38-42, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28697408

RESUMO

Trisomy X (47, XXX) is a sex chromosome aneuploidy condition in which females have an extra X chromosome, compared to the 46, XX karyotype in typical females. There is considerable variation in the phenotype, with some individuals very mildly affected and others with more significant physical and psychological features. However, the trisomy X in this case, without any of these phenotype, is rarely reported. Here, we report a case found during DNA sample collection in a study of genetic polymorphism analysis of loci in Chinese ethnic group, of a female with neither laboratory or clinical signs of Triple X syndrome. She was born at her mother's 60years old and her father's 62years old. Advanced maternal age was found acting as a significant risk factor of Triplo-X. Moreover, her child are also born without manifestations of 47, XXX syndrome. Pedigree study demonstrated the normal karyotype of the children. A diagnosis of 47XXX was made on the basis of a chromosomal study. Therefore, laboratory investigations (including PCR amplification, more than two kinds of X-STR genotyping, G-banding karyotyping analysis and Pedigree study) are applied to rule out the possibility of Mosaicism (45, X0/47, XXX) and ascertain her 47XXX karyotype without mosaic. The objective of this study was to report a case of trisomy X, diagnostic investigation and management of the case, and to analysis the genetically possible reasons behind the case. To our knowledge, this case is a rare one, found in DNA sample collection for the estimation of gene frequency in the process of genetic polymorphism study, of non-mosaic 47, XXX without signs of physical syndrome and born healthy children. In this study, it revealed that the proportion of trisomy X would be more than official statistics and risk of systemic disabilities is lower than estimated. Moreover, we found out that sample mixture and mosaicism act as the interference factors in forensic test. Therefore, we draw the conclusion that attentions and certain improved methods should be applied to the diagnosis of non-mosaic triple X, which is of great significance in decreasing the interruptions in the whole process of forensic and paternity identification.


Assuntos
Polimorfismo Genético , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Trissomia/diagnóstico , Trissomia/genética , Cromossomos Humanos X/genética , Genética Forense , Genótipo , Humanos , Mosaicismo , Polimorfismo Genético/genética , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/fisiopatologia , Trissomia/fisiopatologia
13.
Eur J Hum Genet ; 25(8): 930-934, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28612834

RESUMO

Sex chromosome aneuploidies (SCA) is a group of conditions in which individuals have an abnormal number of sex chromosomes. SCA, such as Klinefelter's syndrome, XYY syndrome, and Triple X syndrome are associated with a large range of neurological outcome. Another genetic event such as another cytogenetic abnormality may explain a part of this variable expressivity. In this study, we have recruited fourteen patients with intellectual disability or developmental delay carrying SCA associated with a copy-number variant (CNV). In our cohort (four patients 47,XXY, four patients 47,XXX, and six patients 47,XYY), seven patients were carrying a pathogenic CNV, two a likely pathogenic CNV and five a variant of uncertain significance. Our analysis suggests that CNV might be considered as an additional independent genetic factor for intellectual disability and developmental delay for patients with SCA and neurodevelopmental disorder.


Assuntos
Deficiências do Desenvolvimento/genética , Deficiência Intelectual/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Transtornos dos Cromossomos Sexuais/genética , Trissomia/genética , Cariótipo XYY/genética , Cromossomos Humanos X/genética , Variações do Número de Cópias de DNA , Deficiências do Desenvolvimento/diagnóstico , Feminino , Humanos , Deficiência Intelectual/diagnóstico , Masculino , Fenótipo , Aberrações dos Cromossomos Sexuais , Transtornos dos Cromossomos Sexuais/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Trissomia/diagnóstico , Cariótipo XYY/diagnóstico
14.
Genome Biol Evol ; 9(4): 945-955, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28369492

RESUMO

Using molecular chromosomal analyses, we discovered night monkey hybrids produced in captivity from matings between a female Aotus azarae boliviensis (2n = 50) and a male Aotus lemurinus griseimembra (2n = 53). The parents produced seven offspring in total, including one male and six females-a pattern consistent with Haldane's rule. Chromosomal studies were conducted on four of the hybrid offspring. Two of them showed relatively "simple" mixture karyotypes, including different chromosome numbers (2n = 51, 52), which were formed because of a heteromorphic autosome pair in the father (n = 26, 27). The other two hybrid monkeys exhibited de novo genomic and karyotypic alterations. Detailed analysis of the alterations revealed that one individual carried a mixture karyotype of the two parental species and an X chromosome trisomy (53,XXX). The second individual displayed trisomy of chromosome 18 (52,XX,+18) and a reciprocal translocation between autosomes 21 and 23 (52,XX,+18,t(21;23)). Interestingly, the second monkey exhibited mosaicism among blood cells (mos52,XX,+18[87]/52,XX,+18,t(21;23)[85]), but only a single karyotype (52,XX,+18) in skin fibroblast cells. The X- and 18-trisomies were derived from a doubling of the mother's chromosomes in early embryonic cell division, and the reciprocal translocation likely developed in the bone marrow of the offspring, considering that it was observed only in blood cells. Such occurrence of trisomies in hybrid individuals is a unique finding in placental mammals.


Assuntos
Aotidae/genética , Primatas/genética , Cromossomo X/genética , Animais , Bandeamento Cromossômico , Cromossomos Humanos X/genética , Feminino , Fibroblastos , Humanos , Hibridização Genética , Cariotipagem , Masculino , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Trissomia/genética
15.
Acta Med Indones ; 49(1): 17-23, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28450650

RESUMO

AIM: to detect Y-chromosomal microdeletion in Indonesian men with azoospermia or severe oligozoospermia using multiplex PCR. METHODS: we performed 2 multiplex PCR amplifications of the Azoospermia Factor (AZF) region in 71 men. Criteria for including a patient were fulfilled if they presented with azoospermia or severe oligozoospermia, with or without additional abnormalities of sperm motility or of head morphology, raised or normal levels of FSH, normal levels of LH and testosterone, and with no evidence of testicular tumors or other abnormalities. Five men participated as control persons. RESULTS: partial deletion of AZFa was found in 11 men (15.49%), complete deletion of AZFb in 1 man (1.4%), and complete deletion of AZFc in 1 man (1.4%). The unspecific type of deletion was also detected, including the DBY gene in 2 men (2.81%), and partial deletion of both AZFa and AZFb in 2 men (2.81%). No AZF deletion was observed in the control probands. Related to the type of deletion, the AZFa and AZFb deletion showed spermatogenesis arrest in most tubules, while deletion of the DBY gene is associated with the sertoli cell only (SCO) syndrome. CONCLUSION: the frequency of partial deletion of AZFa was found to be relatively high in our center. The type of deletion is associated with the testicular histology.


Assuntos
Azoospermia/genética , Infertilidade Masculina/genética , Oligospermia/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Testículo/patologia , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Deleção Cromossômica , Cromossomos Humanos Y/genética , Humanos , Indonésia , Masculino , Reação em Cadeia da Polimerase Multiplex , Aberrações dos Cromossomos Sexuais , Espermatozoides/fisiologia
16.
Andrology ; 5(4): 691-694, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28395120

RESUMO

Deletions on the long arm of the Y chromosome are a well-known cause of male infertility and it is generally accepted that deletions involving the AZFb region are not compatible with sperm production. Here, we report on two patients for whom basic diagnostic tests showed a deletion of the AZFb region. Unexpectedly, both patients had some residual sperm production. Subsequently, extension and additional analyses of the AZFb region disclosed an aberrant deletion pattern. Therefore, these results emphasize the need for a detailed and powerful analysis of cases where first-line Yq deletion tests reveal an AZFb deletion. Moreover, our study clearly demonstrated that only a very careful selection of test markers will avoid the pitfall of a 'no further treatment possible' wrongful conclusion.


Assuntos
Cromossomos Humanos Y , Fertilidade/genética , Infertilidade Masculina/genética , Oligospermia/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Espermatogênese/genética , Deleção Cromossômica , Cromossomos Humanos Y/genética , Predisposição Genética para Doença , Humanos , Masculino , Reação em Cadeia da Polimerase Multiplex , Oligospermia/diagnóstico , Oligospermia/fisiopatologia , Oligospermia/terapia , Fenótipo , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Risco , Índice de Gravidade de Doença , Aberrações dos Cromossomos Sexuais , Contagem de Espermatozoides , Motilidade Espermática
17.
Reprod Biomed Online ; 34(1): 75-81, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28341418

RESUMO

Male infertility is a major health problem worldwide. Oligospermia and azoospermia are the most common symptoms of this disorder. Despite recent advances, the aetiopathogenesis of defective spermatogenesis remains largely uncertain. The aim of this study is to discover unknown or novel chromosome aberrations associated with male reproductive failure. We developed a high-resolution custom array comparative genomic hybridization for initial screening of copy number variations in 10 patients with idiopathic oligozoospermia and azoospermia and eight normal fertile men. We found that deletions were mainly located in the deleted-in-azoospermia subregion and were confined to patients. More importantly, an interesting microdeletion of the Y chromosome designated as D01 was detected in four out of 10 patients with oligozoospermia and azoospermia. We validated this recurrent deletion in nine out of 100 additional infertile men using polymerase chain reaction assays, whereas, it was not present in 100 proven fertile controls(P = 0.002). Furthermore, a bioinformatics analysis demonstrated that the 5' terminal of D01 is situated proximal to several conserved transcription factor binding sites within the Y chromosome. Our study indicated that this newly identified Y chromosome deletion might be potentially associated with impaired spermatogenesis and it is worthy of further investigations in larger cohorts.


Assuntos
Infertilidade Masculina/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Espermatogênese/genética , Adulto , Deleção Cromossômica , Cromossomos Humanos Y/genética , Hibridização Genômica Comparativa , Humanos , Masculino , Aberrações dos Cromossomos Sexuais , Adulto Jovem
18.
J Int Med Res ; 45(2): 621-630, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28357876

RESUMO

Objective To explore the feasibility of high-throughput massively parallel genomic DNA sequencing technology for the noninvasive prenatal detection of fetal sex chromosome aneuploidies (SCAs). Methods The study enrolled pregnant women who were prepared to undergo noninvasive prenatal testing (NIPT) in the second trimester. Cell-free fetal DNA (cffDNA) was extracted from the mother's peripheral venous blood and a high-throughput sequencing procedure was undertaken. Patients identified as having pregnancies associated with SCAs were offered prenatal fetal chromosomal karyotyping. Results The study enrolled 10 275 pregnant women who were prepared to undergo NIPT. Of these, 57 pregnant women (0.55%) showed fetal SCA, including 27 with Turner syndrome (45,X), eight with Triple X syndrome (47,XXX), 12 with Klinefelter syndrome (47,XXY) and three with 47,XYY. Thirty-three pregnant women agreed to undergo fetal karyotyping and 18 had results consistent with NIPT, while 15 patients received a normal karyotype result. The overall positive predictive value of NIPT for detecting SCAs was 54.54% (18/33) and for detecting Turner syndrome (45,X) was 29.41% (5/17). Conclusion NIPT can be used to identify fetal SCAs by analysing cffDNA using massively parallel genomic sequencing, although the accuracy needs to be improved particularly for Turner syndrome (45,X).


Assuntos
Aneuploidia , DNA/genética , Síndrome de Klinefelter/diagnóstico , Síndrome de Noonan/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos dos Cromossomos Sexuais/diagnóstico , Trissomia/diagnóstico , Cariótipo XYY/diagnóstico , Adulto , Cromossomos Humanos X/genética , DNA/sangue , Feminino , Feto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cariotipagem , Síndrome de Klinefelter/sangue , Síndrome de Klinefelter/genética , Síndrome de Klinefelter/patologia , Síndrome de Noonan/sangue , Síndrome de Noonan/genética , Síndrome de Noonan/patologia , Valor Preditivo dos Testes , Gravidez , Segundo Trimestre da Gravidez , Diagnóstico Pré-Natal/estatística & dados numéricos , Aberrações dos Cromossomos Sexuais , Transtornos dos Cromossomos Sexuais/sangue , Transtornos dos Cromossomos Sexuais/genética , Transtornos dos Cromossomos Sexuais/patologia , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/sangue , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/patologia , Cromossomos Sexuais/química , Cromossomos Sexuais/patologia , Trissomia/genética , Trissomia/patologia , Cariótipo XYY/sangue , Cariótipo XYY/genética , Cariótipo XYY/patologia
19.
Mamm Genome ; 28(5-6): 155-165, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28283737

RESUMO

A recently reported deletion of about 40 Mb in length between 6.12/6.57 and 46.73/47.31 Mb on the Y chromosome long arm of the C57BL/6JBomTac inbred strain made us closely examine the strain's breeding history and reproductive characteristics. We verified that the two copies of Rbm31y that are present inside the putative deletion were indeed deleted. This inbred strain presents an expected litter size for a C57BL/6 substrain. In vitro fertilization (IVF) efficiency and breeding efficiencies are comparable to those of the C57BL/6NTac substrain; however, the male/female sex ratio in the C57BL/6JBomTac is mildly skewed towards females. There is an increase in the percentage of sperm shape abnormalities found in C57BL/6JBomTac (35%) versus C57BL/6NTac (11%). The most frequent type of sperm abnormality observed is bent heads (19%). Additionally, there is deregulation of several transcripts expressed in the testes. We determined that this mutation arose in the C57BL/6JBomTac Foundation Colony in 2008, and it was completely fixed in the colony by 2009.


Assuntos
Infertilidade Masculina/genética , Reprodução/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Testículo/metabolismo , Cromossomo Y/genética , Animais , Deleção Cromossômica , Cromossomos Humanos Y/genética , Feminino , Fertilização In Vitro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Aberrações dos Cromossomos Sexuais , Espermatozoides , Testículo/crescimento & desenvolvimento , Testículo/patologia
20.
Eur J Endocrinol ; 176(6): R339-R353, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28274950

RESUMO

Tall stature is defined as a height of more than 2 standard deviations (s.d.) above average for same sex and age. Tall individuals are usually referred to endocrinologists so that hormonal disorders leading to abnormal growth are excluded. However, the majority of these patients have familial tall stature or constitutional advance of growth (generally associated with obesity), both of which are diagnoses of exclusion. It is necessary to have familiarity with a large number of rarer overgrowth syndromes, especially because some of them may have severe complications such as aortic aneurysm, thromboembolism and tumor predisposition and demand-specific follow-up approaches. Additionally, endocrine disorders associated with tall stature have specific treatments and for this reason their recognition is mandatory. With this review, we intend to provide an up-to-date summary of the genetic conditions associated with overgrowth to emphasize a practical diagnostic approach of patients with tall stature and to discuss the limitations of current growth interruption treatment options.


Assuntos
Estatura , Transtornos do Crescimento/diagnóstico , Acromegalia/diagnóstico , Acromegalia/metabolismo , Acromegalia/terapia , Síndrome de Beckwith-Wiedemann/complicações , Síndrome de Beckwith-Wiedemann/diagnóstico , Cromossomos Humanos X/genética , Gerenciamento Clínico , Síndrome do Cromossomo X Frágil/complicações , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/genética , Transtornos do Crescimento/terapia , Lâmina de Crescimento/cirurgia , Homocistinúria/complicações , Homocistinúria/diagnóstico , Homocistinúria/genética , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/genética , Obesidade/complicações , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Síndrome de Sotos/complicações , Síndrome de Sotos/diagnóstico , Síndrome de Sotos/genética , Tireotoxicose/complicações , Trissomia/diagnóstico , Trissomia/genética
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