Molecular analysis of the AGXT gene in Syrian patients suspected with primary hyperoxaluria type 1.

BACKGROUND: Characterization of the molecular basis of primary hyperoxaluria type 1 (PH-1) in Syria has been accomplished through the analysis of 90 unrelated chromosomes from 45 Syrians patients with PH-1 from different regions. METHODS: Alanine glyoxylate aminotransferase (AGXT) gene mutations have been analyzed by using molecular detection methods based on the direct DNA sequencing for all exons of the AGXT gene. RESULTS: Seventeen pathogenic mutations were detected in our patients. Six mutations were novels. The three most frequent mutations were c.33_34insC (p.Lys12fs) in Exon 1, c.584 T < G; p.Met195Arg in exon 5 and c.1007 T > A (p.Val336Asp) in exon 10, with a frequency of 33.3%, 12.2%, and 11.1%, respectively. CONCLUSION: DNA sequencing used in this study can offer a useful method to investigate the mutations in Syrian PH-1 patients, and could offer an accurate tool for prenatal diagnosis and genetic counseling.

Hb Knossos (HBB: c.82G > T), ß-globin CD 5 (-CT) (HBB: c.17_18delCT) and δ-globin CD 59 (-a) (HBD: c.179delA) mutations in a Syrian patient with ß-thalassemia intermedia.

BACKGROUND: Beta thalassemia (ß-thal) is an inherited hemoglobin disorder characterized by reduced synthesis of the hemoglobin that results in microcytic hypochromic anemia. ß-Thalassemia intermedia (TI) is a clinical term of intermediate gravity between the carrier state and ß-thalassemia major (ß -TM). CASE PRESENTATION: We describe a 12-year-old male proband originating from Al-Quneitra province - southwest Syria. Hematological investigations revealed, pallor and anemia (Hb 9 g/dl). The mean cell volume (MCV) 64 fL; mean cell hemoglobin (MCH) 21.8 pg. Capillary electrophoresis (CE) electropherogram revealed low level of Hb A1 (36.2%), high level of Hb F (62.2%) and low level of Hb A2 (1.6%). The proband requires blood transfusion occasionally. Direct DNA sequencing and Polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) for mutations detection were used. The molecular analysis revealed the presence of rare ß+ Hb Knossos codon 27 (G > T) (HBB: c.82G > T) variant associated with ß0 codon 5 [-CT] (HBB: c.17_18delCT) mutation in beta-globin (ß-globin) gene and δ0 codon 59 [-A] (HBD: c.179delA) mutation in delta-globin (δ-globin) gene. The proband tested negative for the common deletional forms of alpha thalassemia (α-thal). Polymorphism of the Xmn-I locus (HBG2: c.-211C > T) revealed that the proband had a homozygous [TT] for Xmn-1 locus. CONCLUSIONS: To our knowledge, this is the first report of beta thalassemia intermedia due to combination of Hb Knossos /codon 5 [-CT] associated with δ0 codon 59 [-A] in Syrian patient. On the other hand, in Syria, ß-thal carriers who have low level of Hb A2 due to decreased δ-chain production, different δ-thal gene mutations must be screened to avoid the failure diagnosis of ß-thal disease.

Investigation of the mtDNA mutations in Syrian families with non-syndromic sensorineural hearing loss.

OBJECTIVE: Hearing loss is a common sensory disorder, and at least 50% of cases are due to a genetic etiology. Several mitochondrial DNA mutations (mtDNA) have been reported to be associated with nonsyndromic hearing loss (NSHL) in different population. However, There is no previous available data about the frequency of mtDNA mutations as etiology for deafness in Syrian. The aim of present study is to investigate the incidence of common mt DNA mutations in our families with congenital hearing loss and not related to the ototoxicity or aminoglycosides. METHODS: A total of 50 deaf families were enrolled in the present study. Direct sequencing and PCR-RFLP methods were employed to detect seven mt DNA mutations, including A1555G, A3243G, C1494T, G3316A, T7510C, A7445G, and 7472insC. RESULTS: Our results revealed a high prevalence of mt DNA mutation (10%) in deaf families (5/50). In surprising, the unexpected mutations were observed. The G3316A mutation was found in 2 families as homoplasmic genotype. Also, we found the homoplasmic and heteroplasmic genotype for the C1494T mutation in two families. In one family the heteroplasmic genotype for T7510C mutation was observed; this family harbor 35delG mutation in GJB2 gene. None of the common mtDNA mutations (A1555G, A3243G) and other mutations (A7445G, 7472insC) were detected here. CONCLUSION: Our findings indicate to significant contribution of the mt DNA mutations in our families with NSHL. The presented data is the first report about mt DNA and it will improve the genetic counseling of hearing impaired in Syrian families.