Introduction: Childhood-onset proximal spinal muscular atrophies (SMAs) are an autosomal recessive, clinically heterogeneous group of neuropathies characterised by the selective degeneration of anterior horn cells. SMA has an estimated incidence of 1 in 10,000 live births. The causative genes are survival motor neuron (SMN) gene and neuronal apoptosis inhibitory protein (NAIP) gene. Deletions of the telomeric copy of SMN gene (SMN1) have been reported in 88.5% to 95% of SMA cases, whereas the deletion rate for NAIP gene (NAIP) is between 20% and 50% depending on the disease severity. The main objective of this study was to genetically characterise the childhood onset of SMA in Iran. Materials and Methods: Molecular analysis was performed on a total of 75 patients with a clinical diagnosis of SMA. In addition to common PCR analysis for SMN1 exons 7 and 8, we analysed NAIP exons 4 and 5, along with exon 13, as a internal control, by bi-plex PCR. Results: The homozygous-deletion frequency rate for the telomeric copy of SMN exons 7 and 8 in all types of SMA was 97%. Moreover, exons 5 and 6 of NAIP gene were deleted in approximately 83% of all SMA types. Three deletion haplotypes were constructed by using SMN and NAIP genotypes. Haplotype A, in which both genes are deleted, was seen in approximately 83% of SMA types I and II but not type III. It was also found predominantly in phenotypically severe group with an early age of onset (i.e., less than 6-month-old). We also report 34 of our prenatal diagnosis. Conclusions: To our knowledge, the present study is the first one giving detailed information on SMN and NAIP deletion rates in Iranian SMA patients. Our results show that the frequency of SMN1 homozygous deletions in Iran is in agreement with previous studies in other countries. The molecular analysis of SMA-related gene deletion/s will be a useful tool for pre- and postnatal diagnostic. Key words: Deletion analysis, Iran, NAIP gene, Prenatal diagnosis, Spinal muscular atrophy, SMN gene
: Mucopolysaccharidosis (MPS) is a rare and heterogeneous metabolic disorder with wide phenotypic distributions throughout the world. This study aimed to determine the genetic polymorphisms, contributing to the most common types of MPS in 19 unrelated Iranian patients. The sequence of the coding region and exon‐intron boundaries of the MPS genes were analyzed by Sanger sequencing method. We used the biochemical and clinical characteristics of MPS subjects for genetic analysis. A novel IDUA variant (c.99T>C, p.H33H), a novel nonsense change (c.514C>T, p.R172*) in exon 5 of IDS gene, c.74G > A (p. p.R24H) in SGSH gene, and three variants including (c.607C>T (p.R203*), c.259G>C (p.A87P), and c.683G>A (p.R228Q)) in NAGLU (n-acetyl-alpha-glucosaminidase) were predicted as novel pathogenic mutations. In conclusion, this study broadened genotypic spectrum of Iranian MPS patients, facilitating the definition of disease-associated mutations, which help to provide a more effective approach in MPS carrier detection.
Background & objectives: Mucopolysaccharidosis IVA (Morquio syndrome type A) is a lysosomal storage disorder caused by a mutation in the GALNS gene located on chromosome 16q24.3 and is inherited in an autosomal recessive manner. To date, more than 300 different mutations associated with MPS IVA, have been reported. Mutational heterogeneity can lead to difficulties in interpretation of molecular testing results, as novel mutations/variants of unknown significance may be detected relatively frequently. The purpose of this study is to analyze the GALNS mutations in Iranian MPS IVA patients. Methods: Mutation screening of the GALNS gene was performed using direct sequence analysis on DNA samples from 8 unrelated Iranian MPS IVA patients. Results: We have identified three novels and four previously reported mutations in 8 Iranian patients. We identified three novel missense mutations including: c.680T>C (p.F227S) in exon 7, c.G949C (p.G317R) and c.956G>C (p.R319T) in exon 9 in three different Iranian MPS IVA patients. Bioinformatics analysis predicted the novel mutations as being diseasecausing. Conclusion:Our findings indicate the molecular heterogeneity of GALNS gene in Iranian patients. We also managed to find three new mutations of MPS IVA in Iranian patients, which are helpful in diagnosis, genetic counseling and prenatal diagnosis in affected families.
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