Recessive distal motor neuropathy with pyramidal signs in an Omani kindred: underlying novel mutation in the SIGMAR1 gene
| Autor: | S Al-Kalbani, Patrick Scott, R Nandhagopal, Douja Meftah |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Adolescent Oman Genes Recessive Consanguinity Gene mutation medicine.disease_cause Muscular Atrophy Spinal 03 medical and health sciences Exon symbols.namesake 0302 clinical medicine medicine Humans Receptors sigma Allele Genetics Sanger sequencing Mutation Respiratory Distress Syndrome Newborn Transition (genetics) business.industry Disease gene identification Pedigree 030104 developmental biology Neurology Codon Nonsense symbols Female Neurology (clinical) business 030217 neurology & neurosurgery |
| Zdroj: | European journal of neurology. 25(2) |
| ISSN: | 1468-1331 |
| Popis: | Background and purpose Distal hereditary motor neuropathy (dHMN) due to sigma non-opioid intracellular receptor 1 (SIGMAR1) gene mutation (OMIM 601978.0003) is a rare neuromuscular disorder characterized by prominent amyotrophic distal limb weakness and co-existing pyramidal signs initially described in a Chinese family recently. We report an extended consanguineous Omani family segregating dHMN with pyramidal signs in an autosomal recessive pattern and describe a novel mutation in the SIGMAR1 gene underlying this motor phenotype. We also provide an update on the reported phenotypic profile of SIGMAR1 mutations. Methods We utilized homozygosity mapping and whole-exome sequencing of leucocyte DNA obtained from three affected members of an Omani family who manifested with a length-dependent motor neuropathy and pyramidal signs. Results We identified a novel C>T transition at nucleotide position 238 (c.238C>T) in exon 2 of the SIGMAR1 gene. Sanger sequencing and segregation analysis confirmed the presence of two copies of the variant in the affected subjects, unlike the unaffected healthy parents/sibling who carried, at most, a single copy. The T allele is predicted to cause a truncating mutation (p.Gln80*), probably flagging the mRNA for nonsense-mediated decay leading to a complete loss of function, thereby potentially contributing to the disease process. Conclusions Our finding expands the spectrum of SIGMAR1 mutations causing recessive dHMN and indicates that this disorder is pan-ethnic. SIGMAR1 mutation should be included in the diagnostic panel of a dHMN, especially if there are co-existing pyramidal signs and autosomal recessive inheritance. |
| Databáze: | OpenAIRE |
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