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Identification of the rare compound heterozygous variants in the NEB gene in a Korean family with intellectual disability, epilepsy and early-childhood-onset generalized muscle weakness.
Jin, Hyun-Seok; Lee, Jong-Bin; Kim, Kyung; Lee, Ki-Young; Choi, Vit-Na; Kim, Jong-Soo; Jeong, Seon-Yong; Yim, Shin-Young.
Afiliación
  • Jin HS; 1] Department of Medical Genetics, Ajou University School of Medicine, Suwon, Republic of Korea [2] Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea.
  • Lee JB; Department of Physical Medicine and Rehabilitation, Ajou University School of Medicine, Suwon, Republic of Korea.
  • Kim K; 1] Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea [2] Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea.
  • Lee KY; 1] Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea [2] Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea.
  • Choi VN; 1] Department of Medical Genetics, Ajou University School of Medicine, Suwon, Republic of Korea [2] Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea.
  • Kim JS; Theragen BiO Institute, Suwon, Republic of Korea.
  • Jeong SY; 1] Department of Medical Genetics, Ajou University School of Medicine, Suwon, Republic of Korea [2] Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea.
  • Yim SY; 1] Department of Medical Genetics, Ajou University School of Medicine, Suwon, Republic of Korea [2] Department of Physical Medicine and Rehabilitation, Ajou University School of Medicine, Suwon, Republic of Korea.
J Hum Genet ; 59(12): 643-7, 2014 Dec.
Article en En | MEDLINE | ID: mdl-25296583
ABSTRACT
We examined a Korean family with complex phenotypes characterized by intellectual disability, epilepsy and early-childhood-onset generalized muscle weakness. Since we did not find any abnormality using several conventional genetic tests for detection of chromosomal aberrations, gene copy number variations and mitochondrial gene mutations, we aimed to identify disease-causing genetic alteration(s) in this family. We conducted whole-exome sequencing (WES) in this family. After filtering the WES data, we compared five exome sequences of two affected siblings, one unaffected sibling and the unaffected parents, and we determined the allele frequency of the identified variants in an Asian population. Finally, we selected one candidate variant pair which is unique in the patients and corresponds to an autosomal recessive genetic model. The two affected siblings had the same compound heterozygous variation in the NEB gene encoding nebulin, which was composed of two different missense variants c.2603T>C (p.L868P) in exon 27 and c.21340C>T (p.R7114W) in exon 143. We confirmed these variations by Sanger sequencing. On the basis of the fundamental role of nebulin in the brain and skeletal muscles, we concluded that this compound heterozygous NEB variation may be a sound candidate for the disease-causing mutation in this family. Since the patients are characterized by generalized muscle weakness together with neurodevelopmental phenotypes, it is suggested that NEB mutations could manifest more diverse phenotypes than those previously described.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Debilidad Muscular / Epilepsia / Discapacidad Intelectual / Proteínas Musculares Tipo de estudio: Diagnostic_studies Límite: Adolescent / Adult / Child / Female / Humans / Male País/Región como asunto: Asia Idioma: En Revista: J Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2014 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Debilidad Muscular / Epilepsia / Discapacidad Intelectual / Proteínas Musculares Tipo de estudio: Diagnostic_studies Límite: Adolescent / Adult / Child / Female / Humans / Male País/Región como asunto: Asia Idioma: En Revista: J Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2014 Tipo del documento: Article