Autosomal recessive primary microcephaly (MCPH) is a rare genetic disorder, leading to the defect of neurogenic brain development. Individuals with MCPH reveal reduced head circumference and intellectual disability. Several MCPH loci have been identified from several populations. Genetic heterogeneity of this disorder represents molecular testing challenge. An 8 yr old female, born from consanguineous parents, was attended to Fardis Central Lab, Alborz, Iran. Based on the reduced circumference and intellectual disability, MCPH was diagnosed. Whole exome sequencing of the patient identified a novel homozygous frameshift mutation (c.2738dupT, p.Cys914fs) in exon 9 Abnormal Spindle-like Microcephaly )ASPM( gene. By Sanger sequencing, segregation analysis showed that both parents were heterozygous carriers for this variant. The novel frameshift mutation likely truncates the protein, resulting in loss of normal function ASPM in homozygous mutation carriers. The study might add a new pathogenic variant in mutations of the ASPM gene as a causative variant in patients with MCPH and might be helpful in genetic counseling of consanguineous families.

BACKGROUND The association between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln gene polymorphism and hepatocellular carcinoma (HCC) has been investigated in several populations. However, the findings are controversial. The aim of this study was to address the association between XRCC1 Arg399Gln polymorphism and HCC in an Iranian population. METHODS We have evaluated the association between XRCC1 Arg399Gln gene polymorphism and HCC in 151 Iranian individuals (50 patients with HCC and 101 healthy matched controls) using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. RESULTS Significant association was found for the XRCC1 A allele and HCC [OR = 1.93, 95% CI (1.16 - 3.25), P = 0.0099]. Also, genotype analysis by SNPStats online software showed a significant association between XRCC1 gene polymorphisms and HCC under co-dominant, dominant, and recessive genetic models. CONCLUSION Our study provides evidence that the XRCC1 Arg399Gln polymorphism may be associated with the risk of HCC development in Iranian population.

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