Novel LAMA2 gene mutations associated with merosin-deficient congenital muscular dystrophy

Background: Merosin-deficient congenital muscular dystrophy [MDC1A] is a rare autosomal recessive genetic disease occurred due to mutations in the LAMA2 gene. This study investigated the molecular genetics of three Iranian MDC1A patients who manifested hypotonia, muscle weakness at birth, elevated levels of creatine kinase, and normal magnetic resonance imaging before the age of six months

Methods: Peripheral blood samples were collected from three unrelated patients and their families after obtaining informed written consents. Genomic DNA was extracted and sequenced using next-generation sequencing, followed by Sanger confirmation

Results:Sequencing results revealed a known missense mutation, c.8665G>A, and two novel heterozygous sequencing variants affecting splicing, c.397-4-c.478del and c.7452-1G>A, in the LAMA2 gene. Reverse transcriptase-PCR analysis showed that a new intronic variant, c.7452-1G>A, produced aberrant splicing pattern in the patient

Conclusions: This study expands the mutation spectrum of LAMA2 and assists in the diagnosis, genetic counseling, and prenatal diagnosis of the affected families

Genetic analysis of Iranian patients with familial hypercholesterolemia

Background: Familial hypercholesterolemia [FH] is a frequent autosomal dominant disorder of lipoprotein metabolism. This disorder is generally caused by mutations in low-density lipoprotein receptor [LDLR], apolipoprotein B 100 [APOB], and proprotein convertase subtilisin/kexin type 9 [PCSK9] genes. In the present study, we aimed at identifying the common LDLR and APOB gene mutations in an Iranian population

Methods: Eighty unrelated Iranian patients with FH entered the study, based on Simon Broome diagnostic criteria. All samples were screened for two common APOB gene mutations, including R3500Q and R3500W, by the means of ARMS-PCR and PCR- RFLP assays, respectively. In addition, exons 3, 4, 9, and 10 of LDLR gene were sequenced in all patients

Results: A novel mutation in exon 3 [C95W] and a previously described mutation in exon 4 [D139H] of LDLR gene were found. Three previously reported polymorphisms in LDLR gene as well as three novel polymorphisms were detected in the patients. However, in the studied population, no common mutations were observed in APOB gene

Conclusion: The results of our study imply that the genetic basis of FH in Iranian patients is different from other populations

[Frequency of TNFalpha-244GA, TNFalpha-308GA and TNFalpha-238GA polymorphisms in healthy and malaria infected patients of Kerman and Hormozgan provinces]

Tumor necrosis factor-alpha [TNF alpha] is one of the key cytokines that affects on pathology of microbial infections. It is suggested that genetic susceptibility to severe form of malaria is associated with TNF alpha promoter polymorphisms. The aim of present study was to investigate frequency of -308 GaA, -244 GaA and -238 GaA polymorphism in 174 samples of Hormozgan and Kerman provinces. In case- control study, we investigated the prevalence of TNF alpha-244 GaA, TNFalpha-308GaA and TNFalpha-238 GaA polymorphism in 174 [154 healthy and 20 patients] individuals from Kerman and Hormozgan provinces of Iran. DNA extraction performed, and then PCR-RFLP was used to detect polymorphisms in -308, -244 and -238 loci. In these three regions, 82.2% of healthy samples showed GG genotype, 14.26% AG and 0.19% AA. All samples of patients showed GG genotype in these three regions. It seems that evolutionary effect of malaria causes increased genotypes which related with protection against malaria or reduction of risk of cerebral malaria and death, although, there was no association between frequency of these genotypes and protection against malaria

Polymorphism analysis of malaria susceptibility biomarkers in G6PD deficiency patients

Several studies suggested that some traits and polymorphisms in human genome such as G6PD deficiency and other genes have protective effects on susceptibility to malaria infection. In present study we investigated the prevalence of TNF alpha -244G -> A, TNF alpha -308G->A,TNF alpha -238G->A, NOS2-954G->C, MBL54G->A, MBL 57G->A, MBLIVS-I-5G->A polymorphisms and G6PD variants [Mediterranean, Chatham, Cosenza, A-[202,376] in 315 subjects with G6PD deficiency and 10 malaria patient. All the 315 subjects were selected from five provinces [Pars, Khuzestan, Esfahan, Yazd and Kerman] and screened by PCR-RFLP method. TheNOS2-954G->A consisted GG[40.31%], GC[53.01%], and CC[6.66%] where as TNF alpha -308 consisted GG[68.8%], AG[31.11%] contents. The TNF alpha -244 showed GG[94.60%], AG[5.39%] genotypes and the TNF alpha -238 had GG[92.69%], AG[6.66%], AA[0.63%] genotypes. The MBL54 polymorphism had GG[75.55%], AG [24.44%], AA[0.63%] genotypes. In MBL 57, had GG[95.23%], AG[4.76%], AA [0.63%] genotypes. The G6PD variants was indicated that Mediterranean mutation in Pars, Khuzestan, Esfahan, Yazd and Kerman provinces was 79.4%, 58%, 83/8%, 64% and 63% respectively and also, the Chatham mutation was 8.8%, 8% 4.5%,3.6% and 0% respectively. Analysis of other four mutations [Cosenza, Arures and A-202 and A-367] showed that none of them had those mutations. Our results suggested that genotypes which causes protection against malaria or reduction of risk for celebral malaria and death has the maximum prevalence in samples taken from the five provinces, but in the kolmogorov-smiranov test results, only NOS2-954G->C supported the theory of relation between these polymorphisms and protection against malaria