Molecular Studies of a Patient with Complete Androgen Insensitivity and a 47,XXY Karyotype

Girardin, Celine; Deal, Cheri; Lemyre, Emmanuelle; Paquette, Jean; Lumbroso, Rose; Beitel, Lenore K.; Trifiro, Mark; Vliet, Guy Van

doi:10.1016/j.jpeds.2009.02.052

Cited by 17 publications

(24 citation statements)

References 16 publications

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“…12 Girardin et al identified a homozygous known missense mutation in exon 5 of the AR gene (c.2560A>T, p.Q733L) in a patient with a 47,XXY karyotype and cAIS. 4 In our KS patient with features including penoscrotal hypospadias, micropenis, and ventral penile chordee abnormalities, we have described a known missense mutation in exon 1 in the AR gene (p.P392S). To date, the p.P392S mutation has been identified in 8 cases (4 penile hypospadias, 1 penoscrotal hypospadias, 1 isolated micropenis, and 2 isolated infertility), which indicated that this mutation, in line with the current case, mostly leads to a mild phenotype in patients with AIS.…”

Section: Discussionmentioning

confidence: 84%

“…[4][5][6][7][8][9][10][11][12] Uehera et al reported a case with 47,XXY and cAIS that had both homozygous nonsense mutations in exon 4 (c.2280c >T, p.Q640X) and in exon 5 (c.2615G>A, p.W751X) of the AR gene. 12 Girardin et al identified a homozygous known missense mutation in exon 5 of the AR gene (c.2560A>T, p.Q733L) in a patient with a 47,XXY karyotype and cAIS.…”

Section: Discussionmentioning

confidence: 99%

“…3 AIS is associated with a variety of phenotypes, ranging from female genitalia (complete AIS, cAIS) to milder degrees of undervirilization (partial AIS, PAIS). 3,4 While a combination of cAIS and 47,XXY has been documented in nine cases, the combination of PAIS and 47,XXY has not been described to date. [4][5][6][7][8][9][10][11][12] We present a 14-month old boy with penoscrotal hypospadias, micropenis, and ventral penile chordee who was found to have a 47,XXY karyotype and a known missense mutation in the AR gene.…”

Section: Introductionmentioning

confidence: 99%

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Identification of an AR mutation in Klinefelter syndrome during evaluation for penoscrotal hypospadias

Acar

Tuhan

Bora

et al. 2017

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Genital anomalies, ranging from female genitalia to milder degrees of undervirilization, are rarely reported in Klinefelter syndrome, in which a male is classically expected to be born with male external genitalia. Though androgen insensitivity syndrome (AIS) is one of the possible pathogenic mechanisms also in Klinefelter syndrome with genital anomalies, to date the AR gene has not been analyzed in any of the published cases of Klinefelter syndrome of the milder phenotype, except for those patients presenting with a severe phenotype, such as female external genitalia. Lack of interest in considering androgen insensitivity in Klinefelter syndrome with a milder phenotype of genital anomalies may impede its identification through an accurate diagnosis. We present a 14-month-old boy with penoscrotal hypospadias, micropenis, and a ventral penile chordee abnormality who was observed to have both a 47,XXY karyotype and a known missense mutation in the AR gene that was inherited from his mother. Although it is recommended that Klinefelter syndrome be considered in the differential diagnosis of penoscrotal abnormalities, mutations in specific genes involved in androgen synthesis or responsiveness should also be investigated.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of an AR mutation in Klinefelter syndrome during evaluation for penoscrotal hypospadias

Acar

Tuhan

Bora

et al. 2017

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“…However, PCR analysis revealed the deleted sequences of AZF region spanding to sYPR3, sY127, sY128, sY130 (AZFb); sY133, sY145, s153, sY152 (AZFd); sY242, sY254, sY157 (AZFc). were diagnosed with androgen insensitivity syndrome [3][4][5][6][7][8][9][10][11]. The remaining cases had different clinical features [12][13][14][15].…”

Section: Resultsmentioning

confidence: 99%

A New Female Case with 47,XXY Karyotype and SRY

Acar¹,

Taşkapu²

2016

Andrology(Los Angel)

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Objective: Numerical abnormalities of sex chromosome, 47,XXY karyotype, have the clinical phenotype of Klinefelter syndrome. Very few 47,XXY cases with a female phenotype have been reported. The testicular feminization syndrome is a female phenotype with a male karyotype (46,XY). Most of these cases have SRY (testisdetermining factor). The genetic explanation of this phenomenon is not very clear. Methods:Clinical examination, conventional cytogenetic analysis, fluorescence insitu hybridization and molecular genetic analysis, polymerease chain reaction (PCR), were done on a 17-year-old female patient.Results: Clinical examination revealed that the case had a female external genitalia, breast development and pubic hair. Some clinical findings of the patients are unique and not similar to the other cases reported in the literature. The present case has different clinical features including normal phenotype, breast development and normal gentelia, tubes, ovaries, but hypoplastic uterus. Cytogenetic analysis and fluorescence in situ hybridization revealed that the Y chromosome was normal; both fluorescence in situ hybridization (FISH) and the polymerase chain reaction (PCR) shown the presence of SRY gene. However, PCR analysis revealed the deleted sequences of AZF region.Conclusion: This is a new distinct female case with 47,XXY in spite of the presence of a Y chromosome and the normal SRY. Undertake published cases in the literature and present case, each case should be considered as a different identity in female phenotype with 47,XXY karyotype and SRY, but the deletion of AZF region on the long arm of chromosome Y.

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“…Seven of these cases have been diagnosed as suffering from androgen insensitivity (testicular feminization) syndrome resulting from mutations in the androgen receptor (AR) gene [German and Vesell, 1966;Bartsch-Sandhoff et al, 1976;Gerli et al, 1979;Müller et al, 1990;Uehara et al, 1999;Saavedra-Castillo et al, 2005;Girardin et al, 2009]. Only 3 cases are reported about women with an additional or at least parts of the Y chromosome.…”

Section: Women With a 47xxy Karyotypementioning

confidence: 99%

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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Molecular Studies of a Patient with Complete Androgen Insensitivity and a 47,XXY Karyotype

Cited by 17 publications

References 16 publications

Identification of an AR mutation in Klinefelter syndrome during evaluation for penoscrotal hypospadias

Identification of an AR mutation in Klinefelter syndrome during evaluation for penoscrotal hypospadias

A New Female Case with 47,XXY Karyotype and SRY

Chromosomal Variants in Klinefelter Syndrome

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