A Comprehensive Overview of NF1 Mutations in Iranian Patients.

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in the NF1 gene. This disorder shows nearly complete penetrance and high phenotypic variability. We used the whole-exome sequencing technique to identify mutations in 32 NF1 cases from 22 Iranian families. A total of 31 variants, including 30 point mutations and one large deletion, were detected. In eight cases, variants were inherited, while they were sporadic in the remaining. Seven novel variants, including c.5576 T > G, c.6658_6659insC, c.2322dupT, c.92_93insAA, c.4360C > T, c.3814C > T, and c.4565_4566delinsC, were identified. The current study is the largest in terms of the sample size of Iranian NF1 cases with identified mutations. The results can broaden the spectrum of NF1 mutations and facilitate the process of genetic counseling in the affected families.

A novel pathogenic variant of BRAT1 gene causes rigidity and multifocal seizure syndrome, lethal neonatal.

INTRODUCTION: Lethal neonatal rigidity and multifocal seizure syndrome (RMFSL) is a severe autosomal recessive epileptic encephalopathy characterized by microcephaly, rigidity, intractable focal seizures, apnea, and bradycardia at or soon after birth. RMFSL is related to BRCA1-associated ATM activator 1 (BRAT1) gene mutations. METHODS: An Iranian couple with history of infant death due to RMFSL was referred to our genetics lab for specialized genetic counseling and testing. Whole Exome Sequencing (WES) was applied. Following WES, Sanger sequencing was performed to confirm the candidate variant. RESULT: A novel nonsense variant (c.2041G > T, p. E681X) was identified in exon 14 of the BRAT1 gene. Based on the American College of Medical Genetics and Genomics guideline this variant was classified as a pathogenic variant. CONCLUSION: This research expands the spectrum of BRAT1 pathogenic variants in RMFSL syndrome and demonstrates the utility of WES in genetic diagnostic.