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Călin Lazăr, Radu Popp, Camelia Al-Khzouz, Gheorghe Mihuț and Paula Grigorescu-Sido

Abstract

Introduction. At the moment there is not enough data in Romania about the incidence of the main genetic mutations which can cause hearing loss.

Objective. The current research aims to determine on a representative sample the prevalence of two mutations of genes GJB2 -c.35delG and p.W24X- and two mutations of genes GJB6 -del(GJB6-D13S1830), del(GJB6-D13S1854) respectively - in patients with congenital nonsyndromic sensorineural hearing loss (CNSHL).

Methods: The sample group included 179 children with CNSHL. The evaluation consist in: a.Clinical, laboratory and imagistic examination; b.ENT exam and audiological evaluation. c.Two methods (semi-nested PCR technique followed by RFLP, validated with ARMS-PCR analysis) for detection of c.35delG and pW24X mutations; d.PCR-multiplex technique for detecting del(GJB6-D13S1830) and del (GJB6-D13S1854).

Results: The audiological diagnosis was: profound hearing loss in 116 patients (64.8%), severe hearing loss in 29 children (16.2%) and moderate hearing loss in 34 patients (representing 19% of the trial patients). The prevalence for the three mutations was: 27.3 % for c.35delG, 3.6 % for p.W24X and 0.28% for del(GJB6-D13S1830). The detection of the three mutations (two on GJB2 gene and one on GJB 6 gene) has allowed to establish the genetic cause for deafness in 45 patients, representing 25.14% of the sample group. Our study is reporting the first case in Romania with a mutation of gene GJB6. Mutation del(GJB6-D13S1854) lacked in all 179 patients.

Conclusion: The prevalence data obtained in the current research are comparable to data communicated by studies from other European countries.

Open access

Cristina Drugan, Tudor Drugan, Catherine Caillaud, Paula Grigorescu-Sido, Tiberiu Nistor and Alexandra M. Crăciun

Abstract

Background: Gaucher disease (GD) is caused by a recessively inherited deficiency of glucocerebrosidase which is encoded by the GBA gene in which nearly 450 mutations have been described. However, only a few genotype- phenotype correlations have been clearly established. The aim of this study was to investigate molecular features of GD in Romanian patients and to evaluate their impact on treatment response. Material and methods: 69 patients, diagnosed between 1997 and 2014 at our national referral laboratory, were included in this study. Frequent point mutations (N370S, L444P, 84GG, R463C) were detected by amplification and restriction enzyme digestion. Recombinant alleles (recTL, recNciI, recA456P) were screened by DNA sequencing. Plasma chitotriosidase served as a biomarker of disease severity throughout the follow-up period. Results: 66 patients had the non-neuronopathic (type 1) form of GD and 3 had the chronic neuronopathic (type 3) phenotype. We identified 79% of the mutant alleles, among which the most frequent mutations were N370S (54%) and L444P (18%). We found a statistically significant (p<0.001) and moderate to good correlation between the total therapeutic dose and the residual chitotriosidase activity (R = 0.621). After two years of treatment, we noticed statistically significant variations in chitotriosidase activity corresponding to the most frequent genotypes (N370S/ unknown allele, N370S/L444P, N370S/N370S and N370S/R463Q). Conclusions: Allele distribution displayed specific features in Romanian GD patients, such as the high prevalence of the N370S allele. Chitotriosidase activity measurement allowed the investigation of genotype influence on treatment outcome.

Open access

Simona Bucerzan, Radu Anghel Popp, Raluca Maria Vlad, Cecilia Lazea, Radu Nicolaescu and Paula Grigorescu-Sido

Abstract

Aim: To assess the risk for trisomy 21 in children, depending on the polymorphisms C677T and A1298C of the methylenetetrahydrofolate reductase (MTHFR) gene in mothers.

Methods: For 93 mothers who have children with trisomy 21 and 202 mothers of healthy children (control group), genotyping of MTHFR polymorphisms C677T and A1298C was performed.

Results: For each polymorphism, three genotypes were identified (normal homozygous, heterozygous and mutant homozygous). For the polymorphism C677T, the frequencies of the three genotypes (CC, CT and TT) were 50.5%, 40.8% and 8.6% in mothers of children with trisomy 21, versus 42.6%, 46% and 11.4% in mothers of healthy children, with no statistically significant differences. The frequency of the polymorphism A1298C was not statistically significant between the two groups for the genotype (AA) (48.4% vs 56.4%) or the genotype (AC) (39.8% vs 38.6%), but the genotype TT was more frequent in mothers of children with trisomy 21 (11.8% vs 4.9%; p = 0.033; OR = 2.57).

Conclusion: Women with genotype CC for the polymorphism A1298C of the MTHFR gene have a 2.57 times higher risk of offspring with trisomy 21.