Clinical characterization of a de novo partial trisomy 22[pter-q12] in a female patient using FISH

Goldenhar sequence is a common birth defect of heterogeneous etiology. Most cases are sporadic. The phenotype is highly variable. Several chromosomal abnormalities have been reported in patients with Goldenhar sequence. In this study we report a 6.5 years old female patient presented clinically with manifestations of Goldenhar sequence. The karyotype revealed a de novo nonmosaic supernumerary marker [47, XX, +mar]. Application of FISH technique using both whole painting chromosome 22 probe and VCF/DGS specific locus probe for 22q11 [N 25 DiGeorge region probe with control, Oncor], showed partial trisomy 22 [22pter22q12]. Comparing our findings with the two previously rare reported cases in literature, the present study strengthens the concept of Goldenhar sequence and trisomy 22 association. Thus, raising the possibility of existence of undetectable gene or genes on 22pter-22q12 region, proposed to be responsible for manifestations of Goldenhar sequence. To our knowledge, this is the first Egyptian case to be reported as having Goldenhar sequence and partial trisomy 22. We recommend combined karyotyping and FISH technique for all cases of Goldenhar sequence to confirm and or clarify this implication for proper genetic counseling

Double aneuploidy in three Egyptian patients: Down- Turner and Down- Klinefelter syndromes

The co-occurrence of two numerical chromosomal abnormalities in same individual [double aneuploidy] is relatively rare and its clinical presentations are variable depending on the predominating aneuploidy or a combination effect of both. Furthermore, double aneuploidy involving both autosomal and sex chromosomes is seldom described. In this study, we described three patients with double aneuploidy involving chromosome 21 and sex chromosomes. They all had the classical non disjunction trisomy 21; that was associated with monosomy X in two of them and double X in the other. Clinically, they had most of the phenotypic features of Down syndrome as well as variable features Characteristic of Turner or Klinefeiter syndrome. Cytogenetic studies and fluorescence in situ hybridization [FISH] analysis were carried out for all patients and their parents. The first patient was a male, mosaic with 2 cell lines [45, X / 47, XY, +21] by regular banding techniques and had an affected sib with Down syndrome [47, XY, +21]. The second was a female mosaic [46, X, +21 / 47, XX, +21] where monosomy X was detected only by FISH in 15% of cells, nevertheless, stigmata of Turner syndrome was more obvious in this patient. The third patient had non mosaic double trisomy, Down-Klinefelter [48, XXY, +21] presented with Down syndrome phenotype. Parental karyotypes and FISH studies for these patients were normal with no evidence of mosaicism. In this report, we reviewed variable clinical presentations among the few reported cases with the same aneuploidy in relation to ours. Also, the proposed mechanisms of double aneuploidy and the occurrence of non-disjunction in more than one family member were discussed. This study emphasizes the importance of molecular cytogenetics techniques for detection of mosaicism, furthermore, we recommend studying of more than one tissue in cases with atypical features of characteristic chromosomal aberration syndromes

Structural abnormalities of the Y chromosome: Genotype-phenotype correlation

The aim of this study was to correlate the structural abnormalities of the Y chromosome to its presenting clinical features to evaluate the phenotype-genotype correlation. The study was performed on 30 patients who had structural Y chromosome abnormalities. The cytogenetic methods included conventional G-banding, diamidino-2-phenylindole [DAPI] and fluorescent in situ hybridization [FISH] techniques. The structural abnormalities of the Y chromosome were a deletion of the long arm [Yq-] in 13 cases, a partial deletion of the short arm [Yp-] in 6 cases, large heterochromatin of Y [Yq+] in 6 cases, pericentric inversion in 4 cases and one case with ring Y. Their phenotypic presentations varied from complete normal male, ambiguous genitalia to complete female phenotype. The clinical presentations and cause of referral of the patients were variable including male infertility and azoospermia, primary amenorrhea, mental retardation, multiple congenital anomalies and/or dysmorphism, short stature, ambiguous genitalia, routine premarital counseling and repeated abortions