Atypical XX male with the <i>SRY</i> gene located at the long arm of chromosome 1 and a 1qter microdeletion

Queralt, Rosa; Madrigal, Irene; Vallecillos, M. Angeles; Morales, Carme; Ballescá, José-Luis; Oliva, Rafael; Soler, Anna; Sánchez, Aurora; Margarit, Ester

doi:10.1002/ajmg.a.32284

Cited by 28 publications

(18 citation statements)

References 12 publications

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“…It was postulated that the translocation between the SRY carrying Y chromosome and an autosomal chromosome was due to nonhomologous recombination between the autosomal chromosome and Ypter (containing SRY locus) during paternal meiosis [Queralt et al, 2008;Chien et al, 2009]. Regarding the phenotype there are no differences between the patients with the SRY gene on the X chromosome and the patients carrying the SRY gene on an autosomal chromosome.…”

Section: Men With a 46xx Karyotype Including Patients With Ambiguousmentioning

confidence: 76%

“…Only 3 cases have been described in the literature about 46,XX men with SRY located on an autosomal chromosome [Dauwerse et al, 2006;Queralt et al, 2008;Chien et al, 2009]. It was postulated that the translocation between the SRY carrying Y chromosome and an autosomal chromosome was due to nonhomologous recombination between the autosomal chromosome and Ypter (containing SRY locus) during paternal meiosis [Queralt et al, 2008;Chien et al, 2009].…”

Section: Men With a 46xx Karyotype Including Patients With Ambiguousmentioning

confidence: 99%

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Chromosomal Variants in Klinefelter Syndrome

Frühmesser

Kotzot²

2011

Sex Dev

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Klinefelter syndrome (KS) describes the phenotype of the most common sex chromosome abnormality in humans and occurs in one of every 600 newborn males. The typical symptoms are a tall stature, narrow shoulders, broad hips, sparse body hair, gynecomastia, small testes, absent spermatogenesis, normal to moderately reduced Leydig cell function, increased secretion of follicle-stimulating hormone, androgen deficiency, and normal to slightly decreased verbal intelligence. Apart from that, amongst others, osteoporosis, varicose veins, thromboembolic disease, or diabetes mellitus are observed. Some of the typical features can be very weakly pronounced so that the affected men often receive the diagnosis only at the adulthood by their infertility. With a frequency of 4%, KS is described to be the most common genetic reason for male infertility. The most widespread karyotype in affected patients is 47,XXY. Apart from that, various other karyotypes have been described, including 46,XX in males, 47,XXY in females, 47,XX,der(Y), 47,X,der(X),Y, or other numeric sex chromosome abnormalities (48,XXXY, 48,XXYY, and 49,XXXXY). The focus of this review was to abstract the different phenotypes, which come about by the various karyotypes and to compare them to those with a ‘normal’ KS karyotype. For that the patients have been divided into 6 different groups: Klinefelter patients with an additional isochromosome Xq, with additional rearrangements on 1 of the 2 X chromosomes or accordingly on the Y chromosome, as well as XX males and true hermaphrodites, 47,XXY females and Klinefelter patients with other numeric sex chromosome abnormalities. In the latter, an almost linear increase in height and developmental delay was observed. Men with an additional isochromosome Xq show infertility and other minor features of ‘normal’ KS but not an increased height. Aside from the infertility, in male patients with other der(X) as well as der(Y) rearrangements and in XXY women no specific phenotype is recognizable amongst others due to the small number of cases. The phenotype of XX males depends on the presence of SRY (sex-determining region Y) and the level of X inactivation at which SRY-negative patients are generally rarely observed.

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Section: Men With a 46xx Karyotype Including Patients With Ambiguousmentioning

confidence: 76%

Section: Men With a 46xx Karyotype Including Patients With Ambiguousmentioning

confidence: 99%

Chromosomal Variants in Klinefelter Syndrome

Frühmesser

Kotzot²

2011

Sex Dev

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“…Between 80% and 90 % of the 46XX males have a translocation of the SRY region of the short arm of the Y chromosome, usually to the long arm of the chromosome X. Translocation of SRY to autosomes is very rare, but cases have been described in which the SRY was located on chromosome 16 (6) or 1 (1). The rest of the 46 XX males, in which no chromosome Y fragment could be identified, are probably caused by up-regulating mutations or duplication of autosomal genes involved in the development of the testis, like SOX9 on chromosome 17 (1, 2).…”

Section: Discussionmentioning

confidence: 99%

“…The frequency of 46XX males is about 1:20.000 live birth. Most of these cases are caused by the translocation of the SRY genes to an X chromosome, but some are SRY negative, determined by duplications of SOX9, 22q or RSPO1 defects or gonadal mosaicism (1,2). Usually these patients are discovered as adults because of almost normal phenotype (abnormalities include smaller height, gynaecomastia) and diagnosis is postponed until infertility and hypergonadic hypogonadism develop.…”

Section: Introductionmentioning

confidence: 94%

complete sex reversal: sry positive 46,XX male by Y to X translocation

Procopiuc¹

2009

Acta Endo (Buc)

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Individuals with male phenotypes and 46 XX karyotype appear in about 1 of 20,000 births with clinical features varying from normal male appearance to sexual ambiguity and hermaphroditism. More than 80% of these patients present a spontaneous translocation of the SRY gene from the Y to the X chromosome in the paternal germinal cells.We present a case of a 2 years old boy diagnosed with minor hypospadias, bifid scrotum, normal penis and palpable gonads in the scrotum. The karyotype is 46 XX and FISH analysis reveals SRY translocation on one of the X chromosomes. Ultrasound exam does not reveal any mullerian structures and a hCG test proves the testes to be functional. A short course of treatment with hCG is recommended in order to induce the proper development of the scotal sac. The patient will need monitoring, in order to identify the development of hypergonadic hypogonadism, which characterizes such patients in later life. This case underlines the importance of comprehensively investigating any patient with even minor genitalia anomalies.

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“…On basis of the analysis and detection of SRY gene, 46, XX male patients can be clinically divided into SRY-positive and the SRY-negative groups (6,7). SRYpositive individuals usually have normal male genitalia, small azoospermic testes and hypergonadotropic hypogonadism (8), and most carry the SRY gene translocated to the X chromosome during paternal meiosis (7,9); however, SRY autosomal translocations have also been reported in some XX males (10)(11)(12). The diagnosis of SRY-positive patients is usually achieved in adulthood during infertility investigation (3).…”

Section: Introductionmentioning

confidence: 99%

46,XX Male - Testicular Disorder of Sexual Differentiation (DSD): hormonal, molecular and cytogenetic studies

Alves

Braid

Coeli

et al. 2010

Arq Bras Endocrinol Metab

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SUMMARYThe XX male syndrome -Testicular Disorder of Sexual Differentiation (DSD) is a rare condition characterized by a spectrum of clinical presentations, ranging from ambiguous to normal male genitalia. We report hormonal, molecular and cytogenetic evaluations of a boy presenting with this syndrome. Examination of the genitalia at age of 16 months, showed: penis of 3.5 cm, proximal hypospadia and scrotal testes. Pelvic ultrasound did not demonstrate Mullerian duct structures. Karyotype was 46,XX. Gonadotrophin stimulation test yielded insufficient testosterone production. Gonadal biopsy showed seminiferous tubules without evidence of Leydig cells. Molecular studies revealed that SRY and TSPY genes and also DYZ3 sequences were absent. In addition, the lack of deletions or duplications of SOX9, NR5A1, WNT4 and NROB1 regions was verified. The infant was heterozygous for all microsatellites at the 9p region, including DMRT1 gene, investigated. Only 10% of the patients are SRY-negative and usually they have ambiguous genitalia, as the aforementioned patient. The incomplete masculinization suggests gain of function mutation in one or more genes downstream to SRY gene. Arq Bras Endocrinol Metab. 2010;54(8):685-9 SUMÁRIO A síndrome do homem XX é uma condição rara na qual o fenótipo da genitália externa pode variar de uma genitália ambígua até uma genitália masculina normal. Este estudo tem por objetivo relatar a avaliação hormonal, molecular e citogenética de um menino com essa síndrome. O exame da genitália externa na idade de 16 meses mostrava: pênis medindo 3,5 cm, hipospadia proximal e testículos tópicos. A ultrassonografia pélvica não visualizou estruturas mullerianas. Cariótipo foi 46,XX. A testosterona sérica não se elevou após o teste de estímulo com gonadotrofina. Biópsias gonadais mostraram túbulos seminíferos, sem evidência de células de Leydig. Estudos moleculares revelaram ausência dos genes SRY, TSPY e DYZ3, bem como ausência de deleção ou duplicação das regiões SOX9, NR5A1, WNT4 e NROB1. A criança era heterozigótica para todos os microssatélites da região 9p, incluindo o gene DMRT1. Apenas 10% dos pacientes com a síndrome do homem 46,XX são SRY-negativos. Nesses casos, a genitália geralmente é ambígua, como corroborado pelo paciente do presente relato. A masculinização incompleta sugere ganho de mutação funcional em um ou mais genes a jusante do gene SRY. Arq Bras Endocrinol Metab. 2010;54(8):685-9

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Atypical XX male with the SRY gene located at the long arm of chromosome 1 and a 1qter microdeletion

Cited by 28 publications

References 12 publications

Chromosomal Variants in Klinefelter Syndrome

Chromosomal Variants in Klinefelter Syndrome

complete sex reversal: sry positive 46,XX male by Y to X translocation

46,XX Male - Testicular Disorder of Sexual Differentiation (DSD): hormonal, molecular and cytogenetic studies

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