Biallelic mutations in ELFN1 gene associated with developmental and epileptic encephalopathy and joint laxity
| Autor: | Yilmaz Yildiz, Can Kosukcu, Kader Karli Oguz, Ceren Günbey, Neşe Vardar Acar, Dilek Yalnizoglu, Ali Dursun, Halil Tuna Akar, Basri Gülbakan, Didem Yücel Yılmaz, R. Köksal Özgül, Ayça Burcu Kahraman |
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| Rok vydání: | 2021 |
| Předmět: |
Joint Instability
Male Signal peptide Adolescent Developmental Disabilities Synaptogenesis Nerve Tissue Proteins Gene mutation Leucine-rich repeat Biology Frameshift mutation symbols.namesake Genetics Humans Child Frameshift Mutation Gene Alleles Cells Cultured Genetics (clinical) Sanger sequencing Homozygote Infant General Medicine Pedigree Phenotype symbols Female Signal transduction Spasms Infantile |
| Zdroj: | European Journal of Medical Genetics. 64:104340 |
| ISSN: | 1769-7212 |
| Popis: | ELFN1, a transmembrane leucine rich repeat protein, is involved in signal transduction in both neural cells and ROD ON-bipolar synaptogenesis. We present three siblings with developmental and epileptic encephalopathy and co-morbidities due to ELFN1 gene mutation; this is the first report in literature defining the human phenotype of ELFN1 gene mutation. Clinical, electrophysiological, and radiological findings along with comprehensive genetic studies of the patients and their family members are presented. Developmental and epileptic encephalopathy, autistic features, pyramidal signs, joint laxity, and dysmorphic features are the characteristic findings of this new clinical entity, involving mainly nervous system and possibly connective tissue. Whole exome sequence analysis followed by Sanger sequencing in all family members revealed disease-causing 8 bp frameshift mutation depicted as NM_001128636.2: c.42_49delGGCCGCCA; p. (Ala15Profs*241) in ELFN1. The variant, located in the signal peptide domain in the ELFN1 gene, was found to be homozygous in three patients, and heterozygous in the parents and three healthy siblings. Segregation analysis in family members together with pathogenicity assessment tools strongly supported the damaging effect of the frameshift variant on the function of the ELFN1 protein. Mutations in ELFN1 gene may be considered in patients with neonatal and infantile-onset epileptic encephalopathy before the full clinical picture is apparent. |
| Databáze: | OpenAIRE |
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