The use of fluorescence in situ hybridization in the diagnosis of hidden mosaicism: apropos of three cases of sex chromosome anomalies

Abstract

FISH has been used as a complement to classical cytogenetics in the detection of mosaicism in sex chromosome anomalies. The aim of this study is to describe three cases in which the final diagnosis could only be achieved by FISH. Case 1 was an 8-year-old 46,XY girl with normal female genitalia referred to our service because of short stature. FISH analysis of lymphocytes with probes for the X and Y centromeres identified a 45,X/46,X,idic(Y) constitution, and established the diagnosis of Turner syndrome. Case 2 was a 21-month-old 46,XY boy with genital ambiguity (penile hypospadias, right testis, and left streak gonad). FISH analysis of lymphocytes and buccal smear identified a 45,X/46,XY karyotype, leading to diagnosis of mixed gonadal dysgenesis. Case 3 was a 47,XYY 19-year-old boy with delayed neuromotor development, learning disabilities, psychological problems, tall stature, small testes, elevated gonadotropins, and azoospermia. FISH analysis of lymphocytes and buccal smear identified a 47,XYY/48,XXYY constitution. Cases 1 and 2 illustrate the phenotypic variability of the 45,X/46,XY mosaicism, and the importance of detection of the 45,X cell line for proper management and follow-up. In case 3, abnormal gonadal function could be explained by the 48,XXYY cell line. The use of FISH in clinical practice is particularly relevant when classical cytogenetic analysis yields normal or uncertain results in patients with features of sex chromosome aneuploidy. Arq Bras Endocrinol Metab. 2012;56(8):545-51

Tumors of Bilateral Streak Gonads in Patients with Disorders of Sex Development Containing Y Chromosome Material

“…It is possible that a difference in screening methods for Y chromosome material may influence the results. Using molecular techniques such as fluorescence in situ hybridization or polymerase chain reaction, the detection of low frequency cell lines and possible structural anomalies is improved (12,13,14). Some authors reported that polymelase chain reaction is more effective than cytogenetic analysis for detecting hidden Y chromosome material (13, 14).…”

Prevalência de sequências do Y e de gonadoblastoma em síndrome de Turner

“…Chromosomal mosaicism is defined as the presence of two or more distinct cell lines within the same individual resulting from post-zygotic nondisjunction. When it occurs in already differentiated cells, mosaicism may be confined to one or a few tissues 26. In this context, investigation of Y-chromosome sequences in tissues of different embryonic origins is advised, such as cells of the oral mucosa, which can easily be harvested by non-invasive procedures.…”

“…Mosaicismo cromossômico é definido como a presença de duas ou mais linhagens celulares diferentes em um mesmo indivíduo resultante de não disjunção pós-zigótica. Quando esse ocorre em células já diferenciadas, o mosaicismo pode ser confinado a um ou poucos tecidos 26. Nesse sentido, a investigação de sequências do cromossomo Y em tecidos com diferentes origens embrionárias é aconselhada, como, por exemplo, as células de mucosa oral, que podem ser facilmente obtidas por procedimentos não invasivos.…”

Disorder of Sexual Development and Congenital Heart Defect in 47XYY: Clinical Disorder or Coincidence?

“…This may explain some cases of infertility in adults with 47XYY. Indeed, the association with infertility problems was reported with scrotal findings ranging from normal to atrophic testicles, oligospermia, and varying endocrine profiles [ 3 , 8 , 10 , 31 ]. It is currently known that some cases with infertility are associated with Yq microdeletions with a significant diagnostic and prognostic value.…”