Clinical and cytogenetic study of a non mosaic 46, X, isodicentric Yq in an Egyptian patient with Turner syndrome.

Summary: Clinical and cytogenetic study of a non mosaic 46, X, isodicentric Yq in an Egyptian patient with Turner syndrome: We report on a female with Turner syndrome phenotype and an isodicentric Y chromosome 46, X, idicYq a combination which has to the best of our knowledge not been reported before.Objective: To delineate the phenotypic spectrum (clinical and gonadal features) for a female patient with 46, X, + marker karyotype.Patients and Methods: The study included a female patient referred to the Clinical Genetics Department, National Research Centre, Egypt. Our patient was subjected to clinical examination and chromosome analysis by GTG banding techniques. Fluorescence in situ hybridization (FISH) was done to identify the marker chromosomes detected by conventional methods.Results: The patient presented with bilateral lymphedema of upper and lower limbs since birth. Craniofacial anomalies (epicanthal folds, broad nasal bridge, long philtrum, protruded tongue, low set ears, short neck), genital ambiguity, with variable Turner stigmata and normal height were detected. Chromosome analysis revealed non mosaic 46, X, + marker. FISH showed 46, X, isodicentric Yq, SRY was negative and deletion of Yp subtelomere.Conclusion: To our knowledge, such an association has not been previously described. Further elucidation to pinpoint the level of the defect of major Y genes is of great clinical significance for better phenotype/karyotype correlations.Key-Words: Ambiguous genitalia - Disorder of sex development - Intersex - Fluorescence In Situ Hybridization.INTRODUCTIONTurner syndrome (TS) affects 1 in approximately 3000 live born females and is thought to be caused by the absence of genes normally present on the second sex chromosome. Abnormalities involving sex chromosomes account for approximately 0.5% of live births (20). The phenotypes of individuals with mosaic cell lines having structural aberrations of the X and Y chromosomes are variable and hard to accurately predict. Phenotypes associated with sex chromosome mosaicism range from Turner syndrome to males with infertility, and often present with ambiguous genitalia (20). Sexual differentiation depends upon a series of complex events that lead to the differentiation of the gonads into testicular tissue and the production and action of androgens. Variations in any of these pathways can lead to conditions where the phenotype and genotype are discordant called disorders of sex development (DSDs). The presence of the Y chromosome will direct testicular development, through a switch gene present on its short arm, called the SRY gene (16). The SRY gene, encodes for a transcription factor and represents the initial genetic switch that directs the bipotential gonad into testis differentiation. Around 1 0-1 5% of all patients with XY gonadal dysgenesis have deletions of or inactivating mutations in SRY gene (3). The representation of Y-chromosome sequences in TS patients reported in the literature is very divergent (mostly between 5% and 10%) (8). All the Y isodicentric chromosomes carry the testis determining gene SRY thought to lie in the Y pericentromeric region (4, 1 1, 21). Isodicentric chromosomes are the most commonly reported aberrations of the human Y chromosome. Among structural abnormalities of the Y-chromosome, isodicentric Y (idicYq) chromosomes are found in 26.5% (17). The idic (Y) are unstable during cell division and can generate various types of cell lines, most reported patients are chromosomal mosaics (95%), generally including a 45, X cell line (9). Only 5% of the patients with die (Y) manifest in non-mosaic form, this event occur probably during spermatogenesis (12). Isodicentric Y chromosomes (idicY) cause several sex-linked phenotypes depending on the location of the breakpoints as well as on the proportion of isodicentric Y in different cell lines and vary from typical Turner syndrome to phenotypic males or individual with ambiguous genitalia (22, 26). …