A novel compound heterozygous NEB mutationin Korean patients with intellectual disability, epilepsy,and acongenital myopathy

I examined a Korean family with complex phenotypes characterized by intellectualdisability,epilepsy,and generalized muscle weakness of early childhood onset. I performed several conventional genetic tests to detect chromosomal aberrations, gene copy number variations, and candidate gene and mitochondrial gene mutations. After finding no abnormality ,I conducted whole exome sequencing (WES)in this family. After filtering the WES data, I compared five exome sequences of two affected siblings, one unaffected sibling, and the unaffected parents, and I determined the allele frequency of the identified variants in an Asian population. Finally, I selected one candidate variant pair corresponding to an autosomal recessive genetic model. The two affected siblings had the same compound hetero zygous mutation in the NEB gene encoding nebulin, which was composed of two different novel missense mutations: c.2603T>C (p.L868P)in exon 27 and c.21340C>T (p.R7114W) in exon 143. As NEB gene mutations are known to cause autosomal recessive myopathies and the patients have generalized muscle weakness together with neurodevelopmental phenotypes, I concluded that this novel compound hetero zygote NEB mutation might be the disease-causing mutation underlying the patients’ clinical phenotypes.

Author dc:creator

• 이, 종빈

Contributors dc:contributor

• 임, 신영
• 대학원 의학과
• 201124371

• congenital myopathy
• epilepsy
• intellectual disability
• quadriplegia
• whole exome sequencing
• mutation
• NEB gene
• nebulin

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000017654
000000017654

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/10933