A novel TBX1 missense mutation in patients with syndromic congenital heart defects.

Congenital heart defects represent a characteristic part of several genetic syndromes associated with chromosomal abnormalities such as 22q11.2 deletion syndrome; many genes located in this locus, mainly TBX1, are candidate genes for congenital heart defects. In our cohort of 27 subjects with congenital heart defect, both karyotype analysis and Fluorescence in situ hybridization (FISH) were performed. The TBX1 gene was sequenced in patients lacking chromosomal abnormalities. FISH analysis showed a de novo 22q11.2 deletion in two patients. The screening of TBX1 coding sequence identified a novel missense mutation c.569C > A (p.P190Q) in six unrelated patients and detected two associated known single nucleotide polymorphisms; the c.664C > T (rs2301558) in three patients and the c.420T > C (p.Phe140 Phe) (rs41298814) in one patient. Bioinformatic tools show that the novel missense mutation c.569C > A could modify the function and the stability of the TBX1 protein. The c.569C > A mutation was not found in 50 healthy controls. Ours results suggest a deleterious role of the c.569C > A mutation and strengthen the hypothesis that this mutation might be responsible for the same phenotype spectrum as the 22q11.2 deletion syndrome.

Polymorphisms of glutathione S-transferases M1, T1, P1 and A1 genes in the Tunisian population: an intra and interethnic comparative approach.

Genetic polymorphisms in glutathione S-transferases (GSTs) genes might influence the detoxification activities of the enzymes predisposing individuals to cancer risk. Owing to the presence of these genetic variants, inter-individual and ethnic differences in GSTs detoxification capacity have been observed in various populations. Therefore, the present study was performed to determine the prevalence GSTM1 0/0, GSTT1 0/0, GSTP1 Ile(105)Val, and GSTA1 A/B polymorphisms in 154 healthy individuals from South Tunisia, and to compare them with those observed in North and Centre Tunisian populations and other ethnic groups. GSTM1 and GSTT1 polymorphisms were analyzed by a Multiplex-PCR approach, whereas GSTP1 and GSTA1 polymorphisms were examined by PCR-RFLP. The frequencies of GSTM10/0 and GSTT1 0/0 genotypes were 53.9% and 27.9%, respectively. The genotype distribution of GSTP1 was 47.4% (Ile/Ile), 40.9% (Ile/Val), and 11.7% (Val/Val). For GSTA1, the genotype distribution was 24.7% (A/A), 53.9% (A/B), and 21.4% (B/B). The combined genotypes distribution of GSTM1, GSTT1, GSTP1 and GSTA1 polymorphisms showed that thirty one of the 36 possible genotypes were present in our population; eight of them have a frequency greater than 5%. To the best of our knowledge, this is the first report of GSTs polymorphisms in South Tunisian population. Our findings demonstrate the impact of ethnicity and reveal a characteristic pattern for Tunisian population. The molecular studies in these enzymes provide basis for further epidemiological investigations in the population where these functional polymorphisms alter therapeutic response and act as susceptibility markers for various clinical conditions.