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1.
Medicine (Baltimore) ; 98(44): e17838, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689873

RESUMO

RATIONALE: Recurrence of Klinefelter syndrome (KS) in non-twin brothers is very rare. This study examined the inheritance pattern of supernumerary X chromosomes in non-twin brothers. PATIENT CONCERNS: A 16-year-old man presented with small-sized testicles. During his diagnostic work-up, his brother, in his late 20's, also complained of small testes and erectile dysfunction. DIAGNOSIS: Chromosome analysis in peripheral blood revealed non-mosaic 47,XXY karyotype in both brothers. Their mother showed a normal 46,XX karyotype. INTERVENTIONS: To examine the inheritance pattern of supernumerary X chromosomes, quantitative-fluorescence PCR was performed with small tandem repeat markers. It revealed that their supernumerary X chromosomes were inherited from different parents. OUTCOMES: After the diagnosis of KS, 2 brothers started to receive testosterone treatment. CONCLUSION: This case report is the first to report differences in the origins of supernumerary X chromosomes in brothers with KS and furthers the current understanding of the cytogenetic mechanisms in KS.


Assuntos
Cromossomos Humanos X , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Adolescente , Adulto , Disfunção Erétil/etiologia , Humanos , Síndrome de Klinefelter/tratamento farmacológico , Masculino , Pais , Reação em Cadeia da Polimerase/métodos , Irmãos , Sequências de Repetição em Tandem , Testosterona/uso terapêutico
2.
Cytogenet Genome Res ; 159(2): 55-65, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31630146

RESUMO

Klinefelter syndrome (KS) is one of the most common congenital disorders of male infertility. Given its high heterogeneity in clinical and genetic presentation, the relationship between transcriptome, clinical phenotype, and associated co-morbidities seen in KS has not been fully clarified. Here, we report a 47,XXY Chinese male with infertility and analyzed the differences in gene expression patterns of peripheral blood mononuclear cells (PBMCs) with regard to a Chinese male and a female control with normal karyotype by single-cell sequencing. A total of 24,439 cells were analyzed and divided into 5 immune cell types (including B cells, T cells, macrophage cells, dendritic cells, and natural killer cells) according to marker genes. Using unsupervised dimensionality reduction and clustering algorithms, we identified molecularly distinct subpopulations of cells between the KS patient and both controls. Gene ontology enrichment analyses yielded terms associated with well-known comorbidities seen in KS as well as an affected immune system and type I diabetes mellitus. Based on our data, we identified several candidate genes which may be implicated in regulating the phenotype of KS. Overall, this analysis provides a comprehensive map of the cell types of PBMCs in a KS patient at the single-cell level, which will contribute to the prevention of comorbidity and improvement of the life quality of KS patients.


Assuntos
Síndrome de Klinefelter/genética , Feminino , Expressão Gênica/genética , Expressão Gênica/imunologia , Genótipo , Humanos , Sistema Imunitário/imunologia , Infertilidade Masculina/genética , Infertilidade Masculina/imunologia , Síndrome de Klinefelter/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/fisiologia , Masculino , Fenótipo , Análise de Célula Única/métodos , Transcriptoma/genética , Transcriptoma/imunologia
3.
Exp Suppl ; 111: 443-473, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588543

RESUMO

Turner and Klinefelter syndromes are the most common chromosome abnormalities compatible with life. Prader-Willi syndrome is a complex multisystem imprinting disorder characterized by hypothalamic dysfunction, neurological implications, and psychiatric disturbances. All three conditions are associated with progressively increasing risk for metabolic and autoimmune morbidity and mortality. This chapter focuses on the endocrine aspects of these syndromes and recent discoveries based on epigenetics and gene expression studies that have broadened our understanding of their extensive phenotypic variability and heterogeneous comorbidities.


Assuntos
Aberrações Cromossômicas , Síndrome de Klinefelter/genética , Síndrome de Prader-Willi/genética , Síndrome de Turner/genética , Humanos
4.
Rev Med Chil ; 147(4): 518-521, 2019 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-31344216

RESUMO

Klinefelter syndrome (47, XXY in most cases) is a frequently underdiagnosed chromosomal anomaly associated with multiple comorbidities in adult life. Patients with Klinefelter syndrome have a higher risk of cancer. Specifically, these patients have a higher risk for mediastinal germ cell tumors. It is estimated that 8% of male patients with mediastinal tumors have Klinefelter. We report a 42-years-old male who suffered recurrent respiratory infections. During the study, a mediastinal mass was found, whose pathological study disclosed a type B thymoma. The patient had a history of infertility, high stature, gynecomastia, obesity with gynecoid distribution of body fat and testicular atrophy. A karyotype was requested (47, XXY), confirming the diagnosis of Klinefelter syndrome.


Assuntos
Síndrome de Klinefelter/patologia , Timoma/patologia , Neoplasias do Timo/patologia , Adulto , Humanos , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Masculino , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/patologia , Radiografia Torácica , Timoma/diagnóstico por imagem , Neoplasias do Timo/diagnóstico , Tomografia Computadorizada por Raios X
5.
Acta Otolaryngol ; 139(6): 479-486, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31035849

RESUMO

BACKGROUND: Usher syndrome (USH) is an autosomal recessive disease characterized by hearing loss, vision loss, and occasionally vestibular dysfunction. Klinefelter syndrome (KS) is an X chromosome polyploidy characterized by one or more additional X chromosomes in males. To date, there has been no report of USH combined with KS. OBJECTIVES: This study examined the causative genes in three Chinese probands with congenital hearing loss. MATERIAL AND METHODS: Targeted next-generation sequencing (NGS) was performed to identify mutations in three probands with hearing loss. Low-coverage whole-genome sequencing (WGS) analysis of aneuploidy was used to verify the chromosome aneuploidy. RESULTS: Four novel MYO7A mutations were identified in two USH1 probands who were initially diagnosed with nonsyndromic hearing loss until the onset of vision loss. Another case was initially diagnosed with nonsyndromic hearing loss and USH2 and KS were discovered incidentally after the genetic analysis. CONCLUSIONS: Our findings expand the mutation spectrum of MYO7A. This is also the first report of concomitant USH and KS. Genetic testing can help with clinical management, particularly if an unrecognized syndromic disorder is identified before the onset of additional symptoms. A clinical genetic evaluation is recommended as part of the diagnostic work-up in congenital hearing loss.


Assuntos
Surdez/genética , Predisposição Genética para Doença , Testes Genéticos/métodos , Síndrome de Klinefelter/genética , Síndromes de Usher/genética , Criança , China , Implantes Cocleares , Surdez/congênito , Feminino , Auxiliares de Audição , Humanos , Síndrome de Klinefelter/diagnóstico , Masculino , Multimorbidade , Mutação , Prognóstico , Amostragem , Síndromes de Usher/diagnóstico
6.
Scand J Immunol ; 90(2): e12776, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31069824

RESUMO

The number of the X chromosome-linked genes has been previously suggested to influence immune responses and the development of autoimmune diseases. In the present study, we aimed at evaluating the level of expression of CD40L (an X-linked gene involved in adaptive immunity) and TLR7 (an X-linked gene involved in innate immunity) in a variety of different karyotypes. Those included males, females and patients with X chromosome aneuploidy. Healthy females (46, XX; n = 10) and healthy males (46, XY; n = 10) were compared to females with Turner syndrome (TS) (45, X; n = 11) and males with Klinefelter syndrome (KS) (47, XXY; n = 5). Stimulation of peripheral blood mononuclear cells (PBMCs) with PMA and ionomycin resulted in higher percentage of CD3 + CD40L+ T cells (P < 0.001) and higher level expression of CD40L in T cell (P < 0.001) in female and KS patients compared with male and TS patients. TLR7-mediated IFN-alpha production by HLADR + CD3- CD19- cells was significantly upregulated in healthy women compared with healthy males, TS and KS patients (P < 0.001). TLR7 agonist-stimulated PBMCs from healthy females and KS patients expressed significantly higher levels of TLR7 mRNA than those from male and TS patients (P < 0.05). The increased expression of the X-linked genes TLR7 and CD40L in healthy females and KS patients suggests that the presence of two X chromosomes plays a major role in enhancing both innate and adaptive immune responses. These results may contribute to the explanation of sex-based differences in immune biology and the sex bias in predisposition to autoimmune diseases.


Assuntos
Imunidade Adaptativa/genética , Ligante de CD40/biossíntese , Ligante de CD40/genética , Cromossomos Humanos X/genética , Dosagem de Genes/genética , Imunidade Inata/genética , Receptor 7 Toll-Like/biossíntese , Receptor 7 Toll-Like/genética , Imunidade Adaptativa/imunologia , Antígenos CD19/biossíntese , Complexo CD3/biossíntese , Células Cultivadas , Variações do Número de Cópias de DNA/genética , Feminino , Humanos , Imunidade Inata/imunologia , Interferon-alfa/biossíntese , Ionomicina/farmacologia , Síndrome de Klinefelter/genética , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Masculino , Ácidos Polimetacrílicos/farmacologia , RNA Mensageiro/biossíntese , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Síndrome de Turner/genética
8.
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
9.
Vnitr Lek ; 65(1): 51-54, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30823838

RESUMO

Acromegaly is a rare disorder usually caused by a benign tumour of the pituitary gland. Long-term presence of elevated growth hormone (GH) and insulin like growth factor 1 (IGF1) levels accompanying this disease is associated with complications such as cardiomyopathy, diabetes mellitus, sleep apnoea and arthropathy. Incidence of acromegaly is 3-4 patients per million per year. Klinefelter syndrome (KS) is the most common sex chromosome disorder occuring in about 1/500 live male births. Common physical features include particularly small testes, among other symptoms are tall stature, reduced muscle tone, delayed pubertal development, lack of secondary male sex characteristics and gynecomastia. We present a 32-year-old man suffering from both acromegaly and 47, XXY Klinefelter syndrome. The patient with typical acromegalic features. Laboratory tests revealed high level of GH which was not suppressed after glucose administration, high level of IGF1, low testosterone concentration with high concentation of luteinizing hormone and follicle stimulating hormone. A magnetic resonance imaging scan revealed a 25 × 18 × 18 mm macroadenoma involving the pituitary gland. A diagnosis of acromegaly was established. After this examination trans-sphenoidal resection was performed. Histopathologic and immunohistochemical findings revealed growth hormoneproducing pituitary adenoma. The presence of infertility with clinical features such as small testes, lack of secondary male sex characteristics and laboratory findings revealed hypergonadotropic hypogonadism that could not be explained by the diagnosis of acromegaly. A chromosomal karyotyping revealed a 47, XXY, confirming the diagnosis of KS. Testosterone replacement therapy wasn´t begun because of patient disagreement Postoperatively elevated plasma concentration of GH and IGF1 levels persist. Treatment by somatostatin analogues (lanreotid) was initiated at dose 120 mg every 28 days. Control magnetic resonance imaging of the sella demonstrated a residue of pituary adenoma size 14 × 14 × 7 mm. The patient is currently undergoing endoscopic revision of the residue. acromegaly - growth hormone - IGF1 - Klinefelter syndrome - testosterone.


Assuntos
Acromegalia , Adenoma , Síndrome de Klinefelter , Neoplasias Hipofisárias , Acromegalia/complicações , Acromegalia/diagnóstico , Acromegalia/genética , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/genética , Adulto , Hormônio do Crescimento Humano , Humanos , Fator de Crescimento Insulin-Like I , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Masculino , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/genética
10.
Andrologia ; 51(5): e13253, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30746732

RESUMO

BACKGROUND: Klinefelter syndrome(KS), affecting 1 in 500-1,000 newborn males, is the most common sex chromosome aneuploidy among males with primary hypogonadism. Isochromosome Xq on the other hand is a rare variant of Klinefelter syndrome, accounting approximately 0.3% of all KS and associated with normal height and androgenisation compared to classical KS. Here, we present a case of isochromosome Xq variant of KS with similar clinical and cytogenetic findings with the few cases reported before. MATERIALS AND METHODS: A 25-year-old male patient referred to our clinic with complaint of infertility. He is the son of a consanguineous couple who are first cousins and there was no family history of reproductive difficulty. In physical examination synophrys, prominent ear and small testicles noted. The patient's spermiogram showed azoospermia and scrotal USG revealed testicular atrophy. RESULTS: Karyotype analysis using G-banding resulted as 47,X,i(X)(q10),Y, and STR analysis showed no deletion in AZF and SRY loci of interest. CONCLUSION: Although several isochromosome Xq variant of KS cases can be found in literature, it is our duty to emphasise the importance of karyotyping for patients with reproductive difficulty who may not have all features of classical Klinefelter syndrome.


Assuntos
Cromossomos Humanos X/genética , Isocromossomos/genética , Síndrome de Klinefelter/genética , Adulto , Humanos , Cariotipagem , Síndrome de Klinefelter/diagnóstico , Masculino
11.
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
12.
BMC Med Genet ; 20(1): 4, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30612561

RESUMO

BACKGROUND: Klinefelter syndrome (KS) is characterized by the presence of at least one supernumerary X chromosome. KS typical symptoms include tall stature, gynecomastia, hypogonadism and azoospermia. KS patients show a higher risk of developing metabolic and cardiovascular diseases, inflammatory and autoimmune disorders, osteoporosis and cancer. Long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) has been shown to be involved in several biologic processes, including inflammatory and autoimmune diseases, vascular endothelial cells apoptosis and atherosclerosis, as well as cellular growth and proliferation, cellular development and cell-to-cell signaling and interaction. The lncRNA GAS5 expression profile in KS patients has never been evaluated so far. METHODS: To accomplish this, GAS5 mRNA levels were evaluated by Next Generation Sequencing (NGS) technology and qRT-PCR assay in 10 patients with KS and 10 age-matched controls. RESULTS: NGS results showed a significantly lncRNAGAS5up-regulation by 5.171-fold in patients with KS. Theresults of qRT-PCR confirmed the NGS data. CONCLUSIONS: These findings showed the occurrence of lncRNA GAS5 over-expression in KS patients. Whether this lncRNA is involved in the pathogenesis of inflammation and autoimmune diseases, atherogenesis or germ cell depletion in KS patients is not known. Further studies are needed.


Assuntos
Regulação da Expressão Gênica , Síndrome de Klinefelter/genética , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , Regulação para Cima , Adulto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , RNA Mensageiro , Doenças Raras/genética , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA
13.
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
14.
J Endocrinol Invest ; 42(7): 833-842, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30499012

RESUMO

PURPOSE: The aim of this study was to study the incidence of Y chromosome microdeletions in a Caucasian population of Klinefelter syndrome (KS) patients and to investigate the possible association between Y chromosome microdeletions and KS. MATERIALS AND METHODS: We conducted a retrospective study on 118 KS patients, 429 patients with non-obstructive azoospermia (NOA), and 155 normozoospermic men. Eight of the 118 KS patients had undergone testicular sperm extraction (TESE). All patients underwent semen examination and Y chromosome microdeletions evaluated by PCR, using specific sequence tagged site (STS) primer sets, which spanned the azoospermia factor AZFa, AZFb, and AZFc regions of the Y chromosome. RESULTS: Semen analysis of the KS group revealed: 1 patient with oligozoospermia, 1 with severe oligoasthenoteratozoospermia, 2 with cryptozoospermia, and 114 with azoospermia. Eight of the 114 azoospermic KS patients underwent TESE, and spermatozoa were recovered from three of these, all of whom had non-mosaic karyotype 47, XXY. 10.7% of the NOA patients presented AZF microdeletions. In 429 cases with NOA, 8 cases had AZFa + b + c deletion, 6 cases had AZF b + c deletion, 4 cases had AZFa microdeletion, 8 cases had AZFb microdeletion, and 20 cases had AZFc microdeletion. Just one KS patient (0.8%) presented microdeletion in the AZFc region. CONCLUSION: The percentage of microdeletions in KS patients was lower than in NOA patients, suggesting that AZF microdeletions and KS do not have a causal relationship and that Y chromosome microdeletions are not a genetic factor linked to KS.


Assuntos
Biomarcadores/análise , Deleção Cromossômica , Cromossomos Humanos Y/genética , Síndrome de Klinefelter/epidemiologia , Síndrome de Klinefelter/genética , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Incidência , Itália/epidemiologia , Síndrome de Klinefelter/patologia , Masculino , Prognóstico , Estudos Retrospectivos
15.
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
16.
Intern Med ; 58(3): 437-440, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30210107

RESUMO

Klinefelter syndrome is a chromosomal disorder with a typical karyotype of 47, XXY, accompanied by various neurological symptoms. We herein report the first case of Klinefelter syndrome with a rare mosaic form of 47, XXY and 48, XXXY, combined with both spastic paraplegia and peripheral motor neuropathy. This case showed spasticity and hyperreflexia with pathological reflexes and ankle clonus as well as muscle weakness in all extremities. A motor nerve conduction study and the magnetic motor evoked potential suggested motor axonal neuropathy and corticospinal tract disorders. The present case suggests that Klinefelter syndrome can present with both upper and lower motor neuron degeneration.


Assuntos
Síndrome de Klinefelter/complicações , Paraplegia/complicações , Doenças do Sistema Nervoso Periférico/complicações , Criança , Humanos , Síndrome de Klinefelter/genética , Masculino
17.
Cancer ; 124(19): 3900-3908, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30291793

RESUMO

BACKGROUND: Males with Klinefelter syndrome (KS) (47,XXY) may be more likely to develop germ cell tumors (GCTs), particularly mediastinal GCTs. To date, there are no reports characterizing the prevalence of KS among male GCT cases. METHODS: The authors used array genotyping data from a Children's Oncology Group epidemiology study to estimate the prevalence of KS in males with GCTs (433 males aged birth-19 years). Using Fisher's exact tests, the authors examined differences in age at diagnosis, race/ethnicity, tumor location and histology, and several birth characteristics between cases of KS-GCT and GCT cases without chromosomal abnormalities. Using publicly available data, the authors estimated the 1-year risk, risk ratio, and corresponding 95% confidence interval of GCTs among KS cases. RESULTS: Based on analysis of array genotyping data, 3% of male GCT cases (13 cases) had KS. The additional X chromosome was of maternal origin in 7 of the 13 cases. Of these 13 KS cases, 5 of 9 KS-GCT cases with parental questionnaire data (56%) reported a diagnosis of KS. No significant differences were observed with regard to patient or birth characteristics between KS-GCT and non-KS-GCT cases. KS-GCT cases were significantly more likely to be diagnosed with mediastinal tumors than non-KS-GCT cases (P<.01). The authors estimated the risk of developing a GCT among males with KS to be 0.00025, or 1 per 4000 males (risk ratio, 18.8; 95% confidence interval, 11.7-30.0). CONCLUSIONS: Compared with males without chromosomal abnormalities, males with KS are more likely to be diagnosed with a mediastinal GCT. The presence of KS should be considered in males with a diagnosis of mediastinal GCT. In the current study, the authors report that approximately one-third of males with mediastinal germ cell tumors have Klinefelter syndrome, and therefore screening of these individuals for the syndrome may be warranted. Males with Klinefelter syndrome are 19 times as likely as males without Klinefelter syndrome to develop germ cell tumors.


Assuntos
Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/epidemiologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Aberrações Cromossômicas/estatística & dados numéricos , Estudos de Coortes , Técnicas de Genotipagem , Homozigoto , Humanos , Lactente , Recém-Nascido , Padrões de Herança/genética , Síndrome de Klinefelter/genética , Masculino , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/epidemiologia , Neoplasias do Mediastino/genética , Neoplasias Embrionárias de Células Germinativas/genética , Adulto Jovem
18.
Am J Mens Health ; 12(6): 2152-2156, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30334491

RESUMO

Klinefelter syndrome (KS) is a common sex chromosome-related abnormality seen among men. KS negatively affects spermatogenesis and testosterone production. It increases the risk of thrombosis but its molecular mechanism has not been well described yet. Elevated PAI-1 is a risk factor for thrombosis. The rs1799889 polymorphism located in the promoter region of the PAI-1 gene was detected in patients with deep venous thrombosis. In this study, the PAI-1 gene variant and its plasma levels in KS patients were examined. Forty-one KS patients (47, XXY) and 50 age-matched healthy controls participated. DNA was isolated from peripheral blood and a real-time PCR method was used to detect known SNPs in the PAI-1 gene. In addition, PAI-1 plasma levels were measured by using ELISA method. There was no significant difference between PAI-1 gene polymorphisms of KS patients and controls ( p > .05). The significant difference was observed in PAI-1 plasma levels between two groups (high PAI-1 plasma level in KS patients compared to controls). The patients' group mean was 55.13 and control group mean in PAI-1 level was 29.89 ng/ml ( p = .020). Clinical features related to thromboembolism especially varicose veins were detected in KS patients frequently ( p = .04). These results suggest that thromboembolism related to clinical features is seen more frequently in cases with KS, but it may not be dependent only on the PAI-1 gene polymorphism structure.


Assuntos
Síndrome de Klinefelter/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Trombofilia/genética , Adulto , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Variação Genética , Humanos , Inibidor 1 de Ativador de Plasminogênio/sangue , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco
19.
Sci Rep ; 8(1): 13740, 2018 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-30213969

RESUMO

Klinefelter syndrome (KS) has a prevalence ranging from 85 to 250 per 100.000 newborn boys making it the most frequent sex chromosome aneuploidy in the general population. The molecular basis for the phenotypic traits and morbidity in KS are not clarified. We performed genome-wide DNA methylation profiling of leucocytes from peripheral blood samples from 67 KS patients, 67 male controls and 33 female controls, in addition to genome-wide RNA-sequencing profiling in a subset of 9 KS patients, 9 control males and 13 female controls. Characterization of the methylome as well as the transcriptome of both coding and non-coding genes identified a unique epigenetic and genetic landscape of both autosomal chromosomes as well as the X chromosome in KS. A subset of genes show significant correlation between methylation values and expression values. Gene set enrichment analysis of differentially methylated positions yielded terms associated with well-known comorbidities seen in KS. In addition, differentially expressed genes revealed enrichment for genes involved in the immune system, wnt-signaling pathway and neuron development. Based on our data we point towards new candidate genes, which may be implicated in the phenotype and further point towards non-coding genes, which may be involved in X chromosome inactivation in KS.


Assuntos
Metilação de DNA/genética , Síndrome de Klinefelter/genética , Inativação do Cromossomo X/genética , Adulto , Cromossomos Humanos X/genética , Feminino , Regulação da Expressão Gênica/genética , Humanos , Recém-Nascido , Síndrome de Klinefelter/patologia , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Transcriptoma/genética
20.
Tijdschr Psychiatr ; 60(9): 606-618, 2018.
Artigo em Holandês | MEDLINE | ID: mdl-30215449

RESUMO

BACKGROUND Klinefelter syndrome (ks) is the most common type of sex chromosome aneuploidy and is associated with psychiatric comorbidities. ks is only diagnosed in less than half of the cases due to the heterogeneous phenotype.
AIM: This study investigates the prevalence of secondary psychiatric diseases and their treatment in ks patients.
METHOD: Relevant articles were identified using the PubMed database. We included articles published in the last ten years, concerning ks patients who were assessed for comorbidities.
RESULTS: A total of 50 articles were included. The most prevalent comorbidities were language disorders and autism spectrum symptoms. Only half the ks population was treated (50.4%) with the primary treatment consisting of hormone therapy. 14% of patients were never treated hormonally.
CONCLUSION: Psychiatric comorbidities were observed in many patients with ks. The early diagnosis of ks in patients is important, given that inadequate treatment of ks patients can lead to reduced social functioning.


Assuntos
Transtorno do Espectro Autista/epidemiologia , Síndrome de Klinefelter/epidemiologia , Síndrome de Klinefelter/psicologia , Transtornos da Linguagem/epidemiologia , Transtorno do Espectro Autista/psicologia , Comorbidade , Humanos , Síndrome de Klinefelter/genética , Transtornos da Linguagem/psicologia
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