Prenatal diagnosis of aneuploidy among a sample of Egyptian high risk pregnancies

A number of studies have shown that aneuploidies of only 5 chromosomes [13, 18, 21, X and Y] account for about 65% of all chromosomal abnormalities and 95% of chromosomal aberrations cause live-born birth defects. Fluorescent in-situ Hybridization [FISH] has been found to be highly effective for rapidly determining the number of specified chromosomes in interphase cells. Prenatal diagnosis was performed on 40 high risk pregnancies chosen from mothers attending the Antenatal Clinic of Ain Shams University Medical genetics Center [ASUMGC]. Early amniocentesis for conventional karyotype analysis of cultured amniocytes and interphase FISH studies of uncultured amniocytes for rapid detection of aneuploidies of chromosomes [13, 18, 21, X and Y] was performed. Normal karyotype was detected in 35 cases [87.5%] and in 4 cases [10%] chromosomal abnormalities were detected by conventional karyotype. However, culture failed in one case [2.5%] due to culture contamination. FISH assay confirmed the cytogenetic findings, for the probes used, on interphase nuclei in all cases analysed, except three cases of structural chromosomal abnormalities: [46, XX, add 21[q22]; 46, XX, t[5; 20] mat, 46, XY inv[9] [p11:q13]] paternal. In one case of culture contamination, FISH analysis was useful in excluding the aberrations of specific chromosomes 13, 18, 21, X and Y on the uncultured/interphase nuclei. Molecular cytogenetic technique of FISH is very useful in urgent cases of prenatal diagnosis where it can be used on uncultured amniocytes for rapid and accurate detection of common aneuploidies

Frequency of fragile-x in x-linked mental retardation

Fragile X syndrome [FXS] is the most common form of inherited mental retardation and accounts for about one third of all cases of X linked mental retardation [XLMR]. It is inherited as an X-linked dominant trait with a fragile site at Xq27.3 locus named fragile X mental retardation gene [FMR-1]. The FMR-1 protein is widely expressed, with the highest expression in brain, testes, ovaries, esophagus, thymus, eye and spleen. This study was conducted on twenty mentally retarded boys aged 8.5 +/- 3.84 years, attending the genetic clinics at Menoufiya University hospitals. They represented 11 families. All patients were subjected to detailed history, family pedigree, anthropometric measurements, thorough clinical examination with clinical scoring for the 13 items fragile X checklist, IQ assessment, routine investigations and cytogenetic studies which included conventional karyotyping using G banding and cytogenetic analysis for fragile X detection. Positive consanguineous marriage was found in 15% of our studied cases. Nine families out of total eleven families had positive family history most of them were second degree relative males through maternal cousins. Craniofacial abnormalities included high arched palate in 65% of patients, large ears in 55%, prominent forehead in 45% and elongated face and abnormal teeth in 30% for each. Speech problems were present in 75% and hyperactivity in 55% of patients. Sixty five percent had mild mental retardation [IQ= 50-70%].By applying the clinical scoring fragile X checklist, it was found that 3 patients [15%] had score more or equal to 19 and 3 [15%] had score from 16 to less than 19, while 14 [70%] had score less than 16. As regards cytogenetic studies, 80% of our patients had normal karyotyping [46 XY] while four cases [20%] had positive fragile site on X-chromosome of whom two cases from the same family had 46, Y, Frg [X] [q27.3], while the other two cases, also from a single family, had inversion of Y chromosome beside positive fragile X chromosome site 46, Fra[X] [q27.3], inv [Y]. So, in a child with isolated mental retardation or autism of unknown etiology with considerable fragile X dysmorphic features or established family history of fragile X syndrome, chromosomal study that identifies the fragile site at Xq27.3 in addition to other cytogenetic abnormalities could be useful or early diagnosis and intervention by a special services team