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1.
Medicine (Baltimore) ; 99(37): e22124, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925763

RESUMO

RATIONALE: This study aimed to report 1 family case with novel Y chromosome structural variations by an established next-generation sequencing (NGS) method using unique STSs. PATIENT CONCERNS: The case studied was from a family with a father and son (the proband). G-band staining was used for karyotype analysis. Y chromosome microdeletions were detected by sequence-tagged site (STS)-PCR analysis and a new NGS screening strategy. DIAGNOSES: Semen analysis showed that the proband was azoospermic. The patient had an abnormal karyotype (45,X[48%]/46,XY[52%]). His father exhibited a normal karyotype. STS-PCR analysis showed that the proband had a deletion of the AZFb+c region, and his father had no deletion of STS markers examined. The sequencing method revealed that the patient had DNA sequence deletions from nt 20099846 to nt 28365090 (8.3 Mb), including the region from yel4 to the Yq terminal, and his father exhibited a deletion of b1/b3 and duplication of gr/gr. INTERVENTIONS: The proband was advised to undergo genetic counseling, and consider the use of sperm from a sperm bank or adoption to become a father. OUTCOMES: The proband was azoospermic. AZFc partial deletions may produce a potential risk for large AZFb+c deletions or abnormal karyotypes causing spermatogenic failure in men. LESSONS: The NGS method can be considered a clinical diagnostic tool to detect Y chromosome microdeletions. The partial AZFc deletions and/or duplications can be a risk of extensive deletions in offspring.


Assuntos
Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Adulto , Deleção Cromossômica , Cromossomos Humanos Y/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cariotipagem , Masculino , Sitios de Sequências Rotuladas , Aberrações dos Cromossomos Sexuais
2.
Braz J Med Biol Res ; 53(3): e8980, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32077464

RESUMO

The mosaic 45,X/46,XY karyotype is a common sex chromosomal abnormality in infertile men. Males with this mosaic karyotype can benefit from assisted reproductive therapies, but the transmitted abnormalities contain 45,X aneuploidy as well as Y chromosome microdeletions. The aim of this study was to investigate the clinical and genetic characteristics of infertile men diagnosed with 45,X/46,XY mosaicism in China. Of the 734 infertile men found to carry chromosomal abnormalities, 14 patients were carriers of 45,X/46,XY mosaicism or its variants, giving a prevalence of 0.27% (14/5269) and accounting for 1.91% (14/734) of patients with a chromosomal abnormality. There were ten cases (71.43%, 10/14) of 45,X mosaicism exhibiting AZF microdeletions. Case 1 and Case 4 had AZFc deletions, and the other eight cases had AZFb+c deletions. A high frequency of Y chromosome microdeletions were detected in male patients with 45,X/46,XY mosaicism. Preimplantation genetic diagnosis should be offered to men having intracytoplasmic sperm injection for hypospermatogenesis caused by 45,X/46,XY mosaicism, to avoid the risk of transfering AZF microdeletions in addition to X monosomy in male offspring.


Assuntos
Infertilidade Masculina/genética , Mosaicismo , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Adulto , China , Deleção Cromossômica , Cromossomos Humanos Y/genética , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Aberrações dos Cromossomos Sexuais
3.
Gene ; 735: 144389, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31982552

RESUMO

Azoospermia factors, located in the long arm of the Y chromosome, are critical for spermatogenesis, the microdeletions of AZF are considered to be associated with male infertility. In addition to complete deletion, several AZFc partial deletions were also detected in infertile men with wide phenotypic heterogeneity. In this study, we investigated the relevance of Y chromosome deletions, Y-linked CNVs and variable phenotypes in infertile men. To clarify the relationship between phenotypic heterogeneity and Y chromosome deletion in male infertility, we performed chromosomal microarray analysis (CMA) capable of analyzing thousands of loci simultaneously to investigate Y-linked copy number variations (CNVs). Firstly, we reviewed the results of Y chromosome screening in 554 infertile patients and then compared the results of CMA to routine Y chromosome screening in 29 patients with Y chromosomal microdeletions. Then, the Y-linked CNVs associated with oligoasthenospermia were identified according to ACMG standards and guidelines. The results indicated that the prevalence of Yq microdeletions was 5.23% (29/554), with 93% (27/29) of the deletions in the AZFc region among 554 infertile men recruited in this study. The results of CMA and multiplex-PCR-based AZFc deletion analysis were generally concordant, but CMA provided more details about location, size and OMIM genes involved in deletion fragments of the AZF region. Of 29 clinically infertile phenotype-related CNVs detected by CMA, nine were pathogenic and the remaining 20 CNVs were OVUS. Except for a 15.69 Mb loss CNV in AZFa + b + c and an 8.25 Mb loss CNV in AZFb + c, others were located in the AZFc region. Based on a combination of the clinical symptoms and loss CNVs, we concluded that the CNV size and the involvement of spermatogenesis critical genes are two important factors that determine the relevance of a CNV in the AZFc region to the presence or absence of a clinically infertile phenotype.


Assuntos
Azoospermia/genética , Variações do Número de Cópias de DNA , Infertilidade Masculina/genética , Oligospermia/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Adulto , Azoospermia/patologia , Deleção Cromossômica , Cromossomos Humanos Y/genética , Humanos , Infertilidade Masculina/patologia , Masculino , Oligospermia/patologia , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/patologia
5.
Cytogenet Genome Res ; 159(3): 137-142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31786569

RESUMO

Chromosomal trisomies are the most frequent major chromosomal anomalies in humans and can be present in a mosaic or a non-mosaic constitution. We report the first case of a newborn girl presenting with multiple congenital anomalies and a double mosaic trisomy involving chromosome 14 and the X chromosome detected by array CGH. Karyotype analysis revealed a double mosaic with 2 independent abnormal cell lines and the absence of 46,XX and 48,XXX,+14 cell lineages. The patient showed most of the clinical characteristics of mosaic trisomy 14. Analysis of autosomal DNA markers in the proband's blood sample did not support the presence of chimerism. Further analysis of chromosome X DNA markers suggests that the extra X chromosome most probably arose as a consequence of nondisjunction in meiosis II in the maternal lineage.


Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos X , Mosaicismo , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Trissomia/genética , Cromossomos Humanos Par 14 , Cromossomos Humanos X/genética , Feminino , Humanos , Recém-Nascido , Aberrações dos Cromossomos Sexuais
6.
Biomedica ; 39(4): 622-630, 2019 12 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31860174

RESUMO

In most cases, male sexual differentiation occurs with SRY gene mediation. However, exceptional genotypes have been identified, as shown in this paper. This was a male adult patient seen at the Servicio de Paternidades, Instituto de Genética, Universidad Nacional de Colombia. The following procedures were carried out: Amelogenin gene and short tandem repeat analyses using human identification commercial kits, conventional karyotype, SRY fluorescent in situ hybridization, PCR analysis for Y chromosome microdeletions, clinical evaluation, and genetic counseling. We present an adult male with unambiguous genitalia, karyotype 46,XX, and an SRY negative and ZFY positive molecular profile. The diagnosis of nonsyndromic 46,XX testicular disorder of sex development (DSD) -a rare genetic condition- was established. Only 20 % of similarly diagnosed patients are SRY negative and exhibit diverse molecular profiles. Until now, available evidence seems to indicate that, even in the absence of SRY, the ZFY factor is involved in male sexual differentiation.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/diagnóstico , Transtornos 46, XX do Desenvolvimento Sexual/genética , Genes sry , Genitália Masculina/anatomia & histologia , Adulto , Amelogenina/análise , Deleção Cromossômica , Cromossomos Humanos Y/genética , Eletroforese Capilar , Genótipo , Humanos , Hibridização in Situ Fluorescente , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Cariotipagem , Fatores de Transcrição Kruppel-Like/análise , Fatores de Transcrição Kruppel-Like/genética , Masculino , Repetições de Microssatélites , Técnicas de Amplificação de Ácido Nucleico , Linhagem , Reação em Cadeia da Polimerase/métodos , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética
7.
Nat Commun ; 10(1): 4897, 2019 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653860

RESUMO

Rare genetic disorders (RGDs) often exhibit significant clinical variability among affected individuals, a disease characteristic termed variable expressivity. Recently, the aggregate effect of common variation, quantified as polygenic scores (PGSs), has emerged as an effective tool for predictions of disease risk and trait variation in the general population. Here, we measure the effect of PGSs on 11 RGDs including four sex-chromosome aneuploidies (47,XXX; 47,XXY; 47,XYY; 45,X) that affect height; two copy-number variant (CNV) disorders (16p11.2 deletions and duplications) and a Mendelian disease (melanocortin 4 receptor deficiency (MC4R)) that affect BMI; and two Mendelian diseases affecting cholesterol: familial hypercholesterolemia (FH; LDLR and APOB) and familial hypobetalipoproteinemia (FHBL; PCSK9 and APOB). Our results demonstrate that common, polygenic factors of relevant complex traits frequently contribute to variable expressivity of RGDs and that PGSs may be a useful metric for predicting clinical severity in affected individuals and for risk stratification.


Assuntos
Estatura/genética , Índice de Massa Corporal , LDL-Colesterol/sangue , Herança Multifatorial , Obesidade/genética , Doenças Raras/genética , Apolipoproteínas B/genética , Transtorno Autístico/genética , LDL-Colesterol/genética , Deleção Cromossômica , Transtornos Cromossômicos/genética , Duplicação Cromossômica/genética , Cromossomos Humanos Par 16/genética , Cromossomos Humanos X/genética , Feminino , Humanos , Hiperlipoproteinemia Tipo II/genética , Hipobetalipoproteinemias/genética , Deficiência Intelectual/genética , Síndrome de Klinefelter/genética , Masculino , Pessoa de Meia-Idade , Pró-Proteína Convertase 9/genética , Receptor Tipo 4 de Melanocortina/deficiência , Receptor Tipo 4 de Melanocortina/genética , Receptores de LDL/genética , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Trissomia/genética , Síndrome de Turner/genética , Cariótipo XYY/genética
8.
Medicine (Baltimore) ; 98(41): e17407, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593094

RESUMO

BACKGROUND: To evaluate the safety of intracytoplasmic sperm injection (ICSI) for men with Y chromosome azoospermia factor (AZF) microdeletions. METHODS: Twenty-five men with Y chromosome microdeletions and their partners underwent ICSI treatment. These subjects were matched against 50 ICSI cycles in which the patients had normal Y chromosomes. RESULTS: Among the 25 couples, 17 achieved a clinical pregnancy of which 14 continued to a live birth. Sixteen men had deletions of AZFc markers (sY152, sY254, and sY255), 1 had a deletion of sY152, 3 had a deletion of sY254, sY255, 1 had a deletion of sY152, sY239, Sy242, sY254, and sY255, and 3 had deletions of sY152, sY254, sY255, and sY157. AZFb microdeletions (sY127, sY134, and sY143) were found in 1 patient. AZF microdeletions had no adverse effects on the clinical pregnancy, implantation or delivery rates, birth weight, gestational age, or sex ratio when compared with the control group. Overall, the multiple gestation and preterm delivery rates of the AZF microdeletion group were similar to those in the control group. CONCLUSION: Men with AZF microdeletions can achieve the delivery of healthy children using ICSI. In this series, it produced good implantation rate and obstetric and perinatal outcomes.


Assuntos
Azoospermia/terapia , Infertilidade Masculina/terapia , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/terapia , Injeções de Esperma Intracitoplásmicas/métodos , Adulto , Azoospermia/genética , Deleção Cromossômica , Cromossomos Humanos Y/genética , Feminino , Humanos , Recém-Nascido , Infertilidade Masculina/genética , Masculino , Gravidez , Resultado da Gravidez , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Resultado do Tratamento
10.
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
11.
J Pak Med Assoc ; 69(4): 567-571, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31000864

RESUMO

This study was designed to investigate the hormonal, seminal changes and chromosomal aberrations in cases of male infertility. A total of ten infertile families from Khyber Pakhtunkhwa of Pakistan were included in the study. The families were clinically evaluated by standard criteria; diagnosis of azoospermic and oligospermic males was confirmed. Seminal, hormonal, ultra sonographic and histopathological examinations were carried out for all the affected participants of the study. Karyotyping was performed on peripheral blood lymphocytes according to standard methods. Hormones were altered in six families. Ultrasonographic abnormal finding was observed in six families. Karyotyping analysis revealed numerical aberration in family G (0X) and family I (XXY). The remainingfamilies had no structural or numerical aberration. Y chromosome microdeletion analysis revealed AZFc deletion in both the affected participants of the family C. The remaining families were found normal for microdeletion. The occurrence of chromosomal anomalies and Y chromosome microdeletions among infertile males strongly suggests the need to include these two tests in routine investigations of male in fertility cases.


Assuntos
Azoospermia/genética , Hipogonadismo/genética , Infertilidade Masculina/genética , Oligospermia/genética , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Adolescente , Adulto , Deleção Cromossômica , Cromossomos Humanos Y/genética , Proteína 1 Suprimida em Azoospermia/genética , Família , Humanos , Infertilidade Masculina/diagnóstico , Síndrome de Klinefelter/diagnóstico , Masculino , Pessoa de Meia-Idade , Linhagem , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Adulto Jovem
12.
Andrologia ; 51(6): e13272, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30907014

RESUMO

In recent years, genetic studies have yielded great progress in elucidating causes of male infertility. This investigation aims to identify frequent genetic abnormalities, that is, sex chromosome aneuploidies and Y-chromosome microdeletions among infertile men in Western Saudi Arabia. From a population of infertile patients, 88 male patients with either azoospermia or severe oligozoospermia (sperm concentration <5 million/ml) were selected. In addition to a thorough clinical workup, karyotypes and Y-chromosomal microdeletions were investigated. Among those 88 infertile patients, we detected six patients with Klinefelter syndrome, two with 47 XYY syndrome and two with Y-chromosome microdeletions AZFb,c. While the prevalence of sex chromosome aneuploidies was in the range of globally investigated populations, the microdeletions appeared to be less frequent in Western Saudi Arabia compared to other regions of the world. All genetically abnormal cases showed sperm concentration <1 million/ml, and hence, this appears to be the threshold for warranting genetic investigations in Western Saudi Arabia. Since Klinefelter and 47 XYY syndromes were only discovered late in life, upon an infertility investigation, sex chromosome aneuploidies due to their many-fold comorbidities require earlier medical attention. A neonatal screening programme is suggested for detection of these aneuploidies in Saudi Arabia for the general health benefit of these patients.


Assuntos
Aneuploidia , Infertilidade Masculina/epidemiologia , Síndrome de Klinefelter/epidemiologia , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/epidemiologia , Adulto , Deleção Cromossômica , Cromossomos Humanos Y/genética , Testes Genéticos/métodos , Necessidades e Demandas de Serviços de Saúde , Humanos , Incidência , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Cariotipagem , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/organização & administração , Pessoa de Meia-Idade , Estudos Prospectivos , Arábia Saudita/epidemiologia , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Contagem de Espermatozoides
13.
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
14.
Genes (Basel) ; 10(2)2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30759861

RESUMO

Mice with deletions of the Y-specific (non-PAR) region of the mouse Y chromosome long arm (NPYq) have sperm defects and fertility problems that increase proportionally to deletion size. Mice with abrogated function of NPYq-encoded gene Sly (sh367 Sly-KD) display a phenotype similar to that of NPYq deletion mutants but less severe. The milder phenotype can be due to insufficient Sly knockdown, involvement of another NPYq gene, or both. To address this question and to further elucidate the role of Sly in the infertile phenotype of mice with NPYq deletions, we developed an anti-SLY antibody specifically recognizing SLY1 and SLY2 protein isoforms and used it to characterize SLY expression in NPYq- and Sly-deficient mice. We also carried out transgene rescue by adding Sly1/2 transgenes to mice with NPYq deletions. We demonstrated that SLY1/2 expression in mutant mice decreased proportionally to deletion size, with ~12% of SLY1/2 retained in shSLY sh367 testes. The addition of Sly1/2 transgenes to mice with NPYq deletions rescued SLY1/2 expression but did not ameliorate fertility and testicular/spermiogenic defects. Together, the data suggest that Sly deficiency is not the sole underlying cause of the infertile phenotype of mice with NPYq deletions and imply the involvement of another NPYq gene.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transporte Vesicular/genética , Infertilidade Masculina/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Espermatogênese/genética , Animais , Deleção Cromossômica , Cromossomos Humanos Y/genética , Fertilidade/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Técnicas de Silenciamento de Genes , Masculino , Camundongos , Camundongos Transgênicos , Aberrações dos Cromossomos Sexuais , Testículo/crescimento & desenvolvimento , Testículo/metabolismo , Testículo/patologia , Cromossomo Y/genética
15.
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
16.
Iran Biomed J ; 23(3): 220-7, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30053768

RESUMO

Background: KDM3A is a key epigenetic regulator expressed in the testis and is required for packaging and condensation of sperm chromatin. To this point, the association of the KDM3A gene with infertility has not been studied in human. The aim of this study was to screen any new mutation in KDM3A gene to explore more details of human male infertility. Methods: In this work, 150 infertile men (oligozoospermia and azoospermia) and 150 normal healthy fathers were studied. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing were used to screen any mutation in exons 12, 22, and 24 of KDM3A. Results: The infertile men showed various SSCP patterns for the exons 12 and 24, but not for exon 22. A transversion point mutation in exon 12 and a single nucleotide deletion in exon 24 were detected using sequencing analysis. The transversion mutation was located in the preceding exon of lysine-specific demethylase1 and Jumonji (Jmj)-C domain and the later one (deletion) in the cupin-like motif of KDM3A protein. Neither Y chromosome microdeletions nor partial azoospermia factor deletion was found in these patients. Conclusion: The mutations found in infertile men with otherwise unexplained severe spermatogenic failure could be considered as the origin of their abnormalities.


Assuntos
Predisposição Genética para Doença , Infertilidade Masculina/genética , Histona Desmetilases com o Domínio Jumonji/genética , Mutação/genética , Adulto , Azoospermia/genética , Sequência de Bases , Deleção Cromossômica , Cromossomos Humanos Y/genética , Éxons/genética , Marcadores Genéticos , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Polimorfismo Conformacional de Fita Simples , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Adulto Jovem
17.
BJU Int ; 123(2): 367-372, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30113756

RESUMO

OBJECTIVE: To describe the prevalence of Y-chromosome microdeletions in a multi-ethnic urban population in London, UK. To also determine predictive factors and a clinical threshold for genetic testing in men with Y chromosome microdeletions. PATIENTS AND METHODS: A retrospective cohort study of 1473 men that were referred to a tertiary Andrology centre with male factor infertility between July 2004 and December 2016. All had a genetic evaluation, hormonal profile and 2 abnormal semen analyses. Those with abnormal examination findings also had targeted imaging performed. RESULTS: The prevalence of microdeletions was 4% (n = 58) in this study. These microdeletions were partitioned into the following regions: Azoospermia factors (AZF); AZFc (75%), AZFb+c (13.8%), AZFb (6.9%), AZFa (1.7%), and partial AZFa (1.7%). A high follicle-stimulating hormone level (P < 0.001) and a low sperm concentration (P < 0.05) were both found to be significant predictors for the identification of a microdeletion. Testosterone level, luteinising hormone level and testicular volume did not predict the presence of a microdeletion. None of the men with an AZF microdeletion had a sperm concentration of >0.5 million/mL. Lowering the sperm concentration threshold to this level retained the high sensitivity (100%) and increased the specificity (31%). This would produce significant cost savings when compared to the European Academy of Andrology/European Molecular Genetics Quality Network and European Association of Urology guidelines. The surgical sperm retrieval (SSR) rate after microdissection testicular sperm extraction was 33.2% in men with AZFc microdeletion. CONCLUSIONS: The prevalence of Y-chromosome microdeletions in infertile men appears to vary between populations and countries. A low sperm concentration was a predictive factor (P < 0.05) for identifying microdeletions in infertile males. A threshold for genetic testing of 0.5 million/mL would increase the specificity and lower the relative cost without adversely affecting the sensitivity. The rate of SSR was lower than that previously described in the literature.


Assuntos
Testes Genéticos , Infertilidade Masculina/genética , Infertilidade Masculina/fisiopatologia , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/fisiopatologia , Contagem de Espermatozoides , Adulto , Deleção Cromossômica , Cromossomos Humanos Y/genética , Hormônio Foliculoestimulante/sangue , Testes Genéticos/economia , Humanos , Infertilidade Masculina/sangue , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Sensibilidade e Especificidade , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/sangue , Adulto Jovem
18.
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
19.
Congenit Anom (Kyoto) ; 59(2): 43-46, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29732662

Assuntos
Aneuploidia , Síndrome de Klinefelter/mortalidade , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/mortalidade , Transtornos dos Cromossomos Sexuais/mortalidade , Síndrome da Trissomía do Cromossomo 18/mortalidade , Cariótipo XYY/mortalidade , Cromossomos Humanos X/química , Cromossomos Humanos X/genética , Cromossomos Humanos Y/química , Permeabilidade do Canal Arterial/genética , Permeabilidade do Canal Arterial/mortalidade , Permeabilidade do Canal Arterial/patologia , Feminino , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/patologia , Comunicação Interatrial/genética , Comunicação Interatrial/mortalidade , Comunicação Interatrial/patologia , Comunicação Interventricular/genética , Comunicação Interventricular/mortalidade , Comunicação Interventricular/patologia , Humanos , Lactente , Recém-Nascido , Cariótipo , Síndrome de Klinefelter/genética , Síndrome de Klinefelter/patologia , Masculino , Aberrações dos Cromossomos Sexuais , Transtornos dos Cromossomos Sexuais/genética , Transtornos dos Cromossomos Sexuais/patologia , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/patologia , Análise de Sobrevida , Trissomia/genética , Trissomia/patologia , Síndrome da Trissomía do Cromossomo 18/genética , Síndrome da Trissomía do Cromossomo 18/patologia , Cariótipo XYY/genética , Cariótipo XYY/patologia
20.
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
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