[Investigation of exon 1 in FXN gene in patients with clinical symptomatic of friedreich ataxia]

Friedreich's ataxia [FRDA] is an autosomal recessive disorder that is typically associated with dysarthria, muscle weakness, spasticity in the lower limbs, scoliosis, bladder dysfunction, absent lower limb reflexes, and loss of position and vibration sense. Approximately two-thirds of these patients suffer from cardiomyopathy and more than 30% have diabetes mellitus. Individuals with FRDA have identifiable mutations in the FXN gene. The most common type of mutation which is observed on both alleles in more than 98% of patients is an expansion of a GAA triplet-repeat in intron of FXN gene. Approximately 2% of individuals with FRDA are compound heterozygotes, who have a GAA expansion in the disease-causing range in one FXN allele and an inactivating FXN mutation in another allele. Aim of the present study was to investigate exon 1 in FRDA gene in patients with clinical symptoms of Friedreich's Ataxia that have not GAA triplet-repeat expansion in intron 1 of FXN gene. In this study, exon 1 in 5 patients suspected of FRDA analyzed using PCR and sequencing. An A to G transition at nucleotide number 815284, in exon 1 was observed in all patients. The results of this study showed that disease-causing homozygous mutations could be because of consanguinity marriage in Iran. Therefore, sequencing of all exons of the gene is necessary

Novel mutations in Sandhoff disease: a molecular analysis among Iranian cohort of infantile patients

Sandhoff disease is an autosomal recessive disorder caused by beta-hexosaminidase deficiency and accumulation of GM2 ganglioside resulting in progressive motor neuron manifestations and death from respiratory failure and infections in infantiles. Pathogenic mutations in HEXB gene were observed which leads to enzyme activity reduction and interruption of normal metabolic cycle of GM2 ganglioside in Sandhoff patients. Six infantile index patients with typical biochemical and clinical picture of the disease were studied at the molecular level. After DNA extraction and amplification, probands and their parents, were evaluated by direct sequencing of amplicons. We identified 7 different mutations among which 4 were novel. The most prevalent finding [50%] among our population was a 16 kb deletion including the promoter and exons 1-5. The other findings included c.1552delG and c.410G>A, c.362 A>G, c.550delT, c.1597c>T, c.1752delTG. We conclude that Cysl37Tyr and R533C mutations may be pathogenic because of changing amino acid and locating at the conserved region and also they have not been observed in hundred controls. Besides, four mutations including: Cysl37Tyr, c.1552delG, c.1597c>T and c.550delT fulfilled almost criteria for pathogenic mutation

novel mutation of GDAP1 associated with Charcot-Marie-tooth disease in an Iranian family

As a result of higher distributed consanguinity in the Mediterranean region and the Middle East, autosomal-recessive forms of Charcot-Marie-Tooth [ARCMT] are more common in these areas. CMT disease caused by mutations in the ganglioside-induced differentiation-associated protein 1 [GDAP1] gene is a severe autosomal recessive neupathy resulting in either demyelinating CMT4A neuropathy or axonal neuropathy with vocal cord paresis. The patient was an 8-year-old boy with AR inheritance that showed some delayed achievement of motor milestones, including walking, also bilateral foot drop, wasting of distal muscles in the legs, pes cavus and marked weakness of the foot dorsiflexors. He had no hoarseness or vocal cord paralysis. Total genomic DNA was extracted from whole peripheral blood of the patient and his family by using standard procedures. PCR- sequencing method were used to analysis the whole coding regions of the GDAP1 gene. A novel homozygote insertion of T nucleotide in codon 34 was detected [c.100_101insT] that probably led to an early stop codon. This mutation may be associated with a common haplotype, suggesting a common ancestor that needs further investigation in the Iranian population