Detection of 22q11.2 deletion among 139 patients with Di George/Velocardiofacial syndrome features.

Cytogenetic and FISH analysis was performed in 139 patients to detect the pathognomonic of Di George/ Velocardiofacial syndrome (DGS/VFCS) deletion 22q11.2. An abnormal karyotype was revealed in 2/139 cases (47, XXY and 46, XX, 2p+). A deletion was found in 17/139 (12.2%) patients (14 males/ 3 females), inherited in 3 (2 maternal and 1 paternal). Patients with 22q11.2 deletion exhibited facial dysmorphic features (82%), congenital heart defects (70%), immunological problems (47%), multiple congenital anomalies (64%), hypocalcemia (47%), mental retardation/learning difficulties (35%), cleft palate/velopharyngeal insufficiency (23.5%), seizures/hypotonia (23%) and growth retardation (12%). Among 56/139 patients with detailed available clinical data, the 22q11.2 deletion was confirmed in all cases with hypocalcemia and in over half of the cases with multiple congenital anomalies, immunological problems and hypotonia/seizures (70%, 60% and 57%, respectively). Genetic reevaluation of 39 patients without the 22q11.2 deletion contributed to the classification of 14 (37%) under different syndromes, emphasizing the need for stricter referral criteria.

Origin of nondisjunction in trisomy 8 and trisomy 8 mosaicism.

Causes of chromosomal nondisjunction is one of the remaining unanswered questions in human genetics. In order to increase our understanding of the mechanisms underlying nondisjunction we have performed a molecular study on trisomy 8 and trisomy 8 mosaicism. We report the results on analyses of 26 probands (and parents) using 19 microsatellite DNA markers mapping along the length of chromosome 8. The 26 cases represented 20 live births, four spontaneous abortions, and two prenatal diagnoses (CVS). The results of the nondisjunction studies show that 20 cases (13 maternal, 7 paternal) were probably due to mitotic (postzygotic) duplication as reduction to homozygosity of all informative markers was observed and as no third allele was ever detected. Only two cases from spontaneous abortions were due to maternal meiotic nondisjunction. In four cases we were not able to detect the extra chromosome due to a low level of mosaicism. These results are in contrast to the common autosomal trisomies (including mosaics), where the majority of cases are due to errors in maternal meiosis.

Partial disomy of Xp and the presence of SRY in a phenotypic female.

We present a study of a mentally retarded and mildly dysmorphic female in whom initial cytogenetic studies identified the karyotype 46,X, + mar. Further characterisation of the structurally abnormal chromosome by fluorescence in situ hybridisation (FISH) showed that it is composed of both X and Y chromosome material with a centromere originating from the Y chromosome. The presence of the DMD gene and the absence of the XIST gene was shown by FISH using locus specific probes. The Y segment included the SRY and ZFY genes. Based on these findings, the karyotype was defined as 46, X,der(Y)t(X;Y) (p21.1;q11). This case illustrates male to female sex reversal owing to a partial duplication of the short arm of the X chromosome in the presence of SRY.

45,X Turner syndrome with normal ovarial function and multiple malformations of the aorta.

We present a case of a female patient with monosomy of X chromosome in peripheral lymphocytes and skin fibroblasts, normal ovarian function and associated multiple congenital abnormalities of the aorta: bicuspid aortic valve, dilatation of the ascending aorta and multiple cystic structures of the aortic wall, complicated by endarteritis. We review the literature on fertile women with 45,X karyotype and the possible pathogenetic mechanisms of the aortic defects described as 'cystic medial necrosis of the aorta'.