Identification of a Novel Homozygous Splice-Site Mutation in SCARB2 that Causes Progressive Myoclonus Epilepsy with or without Renal Failure

• Published in: Chinese medical journal Vol. 131; no. 13; pp. 1575 - 1583
• Main Authors: He, Jin, Lin, Han, Li, Jin-Jing, Su, Hui-Zhen, Wang, Dan-Ni, Lin, Yu, Wang, Ning, Chen, Wan-Jin
• Format: Journal Article
• Language: English
• Published: China Wolters Kluwer India Pvt. Ltd 05.07.2018; Medknow Publications and Media Pvt. Ltd; Lippincott Williams & Wilkins Ovid Technologies; Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, China%Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, China; Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350005, China; Medknow Publications & Media Pvt Ltd; Wolters Kluwer
• Subjects: Ataxia; Diagnosis; Epilepsy; Gene mutation; Genes; Genetic aspects; Genomes; Genomics; High-throughput screening (Biochemical assaying); Homozygosity; Hospitals; Humans; Kidney failure; Laboratories; Lysosomal Membrane Proteins - genetics; Male; Membranes; Mutation; Myoclonic Epilepsies, Progressive - complications; Myoclonic Epilepsies, Progressive - genetics; Myoclonic epilepsy; Neurology; Original; Parkinson's disease; Polymerase chain reaction; Progressive Myoclonus Epilepsies; Progressive Myoclonus Epilepsy with or without Renal Failure; SCARB2 Gene; Targeted Next-Generation Sequencing; Proteins; Receptors, Scavenger - genetics; Renal Insufficiency - complications; Renal Insufficiency - genetics; United States > US; China; California; SCARB2; Gene; Targeted Next-Generation Sequencing; Progressive Myoclonus Epilepsy with or without Renal Failure; Progressive Myoclonus Epilepsies; SCARB2 Gene
• ISSN: 0366-6999; 2542-5641
• DOI: 10.4103/0366-6999.235113

Background: Progressive myoclonus epilepsies (PMEs) comprise a group of rare genetic disorders characterized by action myoclonus, epileptic seizures, and ataxia with progressive neurologic decline. Due to clinical and genetic heterogeneity of PMEs, it is difficult to decide which genes are affected. The aim of this study was to report an action myoclonus with or without renal failure syndrome (EPM4) family and summarize the clinical and genetic characteristics of all reported EPM4 patients. Methods: In the present study, targeted next-generation sequencing (NGS) was applied to screen causative genes in a Chinese PME family. The candidate variant was further confirmed by cosegregation analysis and further functional analysis, including the reverse transcription polymerase chain reaction and Western blot of the proband's muscle. Moreover, literature data on the clinical and mutational features of all reported EPM4 patients were reviewed. Results: The gene analysis revealed a novel homozygous splicing mutation (c.995-1G>A) of the SCARB2 gene in two brothers. Further functional analysis revealed that this mutation led to loss function of the SCARB2 protein. The classification of the candidate variant, according to the American College of Medical Genetics and Genomics standards and guidelines and functional analysis, was pathogenic. Therefore, these two brothers were finally diagnostically confirmed as EPM4. Conclusions: These present results suggest the potential for targeted NGS to conduct a more rapid and precise diagnosis for PME patients. A literature review revealed that mutations in the different functional domains of SCARB2 appear to be associated with the phenotype of EPM4.