Identification of a pathogenic NHLRC1 variant in a consanguineous Pakistani family affected with severe and rapidly progressive Lafora disease  

作　　者：Zain Aslam Bibi Zubaida Ranjha Khan Mazhar Badshah Muhammad Naeem 

机构地区：[1]Medical Genetics Research Laboratory,Department of Biotechnology,Quaid-i-Azam University,Islamabad 45320,Pakistan [2]Department of Neurology and Neurophysiology,Pakistan Institute of Medical Sciences,Islamabad 04485,Pakistan

出　　处：《Acta Epileptologica》2025年第1期124-130,共7页癫痫学报(英文)

基　　金：Zain Aslam(112-36551-2BM1-037);Bibi Zubaida(212-52789-2BM2-080);supported by the Higher Education Commission of Pakistan under Indigenous Ph.D.Fellowships Program.

摘　　要：Background Autosomal recessively inherited progressive myoclonic epilepsy of Lafora,which is also known as Lafora disease,is a fatal neurodegenerative disorder.It affects individuals in late childhood or early adolescence and presents with symptoms of progressive mental and physical deterioration.This disease is caused by pathogenic genetic variants in either of two genes:EPM2A on chromosome 6q24,encoding laforin,or NHLRC1(EPM2B)on chromosome 6p22,encoding malin.Case presentation In this study,we report a clinical and molecular investigation of Lafora disease segregating in a consanguineous Pakistani family.The proband presented with symptoms of rapidly progressive myoclonic epilepsy,but laboratory studies were negative for Lafora bodies and ragged red fibres.Sanger DNA sequencing of the genomic DNA of the proband for EPM2A and NHLRC1 identified a previously reported pathogenic nonsense variant in NHLRC1(NM_198586.3:c.793C>T),which encodes the E3 ubiquitin ligase called malin.The NHLRC1 variant was found in a homozygous state in the proband,predicting a premature stop codon at position 265(NP_940988.2:p.Arg265Ter).If the mRNA escaped nonsense-mediated decay,it would result in a truncated protein lacking 130 amino acids,including three NHL(NCL-1,HT2A,LIN-41)repeats.Conclusions Our study emphasizes the role of molecular genetic testing in patients presenting with symptoms of progressive myoclonic epilepsy.

关 键 词：Progressive myoclonic epilepsy Lafora bodies Laforin DNA sequencing Mutation 

分 类 号：R73[医药卫生—肿瘤]