RESUMEN
Hyperekplexia is commonly familial and with dominant transmission. The gene involved, GLRA1, encodes the alpha1 subunit of the glycine receptor. We describe 3 affected children homozygous for a new mutation, R100H. Both parents were heterozygous carriers; while the father was healthy, the mother has periodic limb movements during sleep. This suggests that Hys-100 could exhibit incomplete penetrance, but was linked to a severe classical form of hyperekplexia in homozygous.
Asunto(s)
Arginina/genética , Histidina/genética , Mutación , Receptores de Glicina/genética , Reflejo Anormal/genética , Adolescente , Análisis Mutacional de ADN/métodos , Salud de la Familia , Femenino , Humanos , MasculinoRESUMEN
Hereditary non-syndromic sensorineural hearing loss (NSSHL) is a genetically highly heterogeneous group of disorders. Autosomal dominant forms account for up to 20% of cases. To date, 39 loci have been identified by linkage analysis of affected families that segregate NSSHL forms in the autosomal dominant mode (DFNA). Investigation of a large Spanish pedigree with autosomal dominant inheritance of bilateral and progressive NSSHL of postlingual onset excluded linkage to known DFNA loci and, in a subsequent genome-wide scan, the disorder locus was mapped to 3q28-29. A maximum two-point LOD score of 4.36 at theta=0 was obtained for marker D3S1601. Haplotype analysis placed the novel locus, DFNA44, within a 3-cM genetic interval defined by markers D3S1314 and D3S2418. Heteroduplex analysis and DNA sequencing of coding regions and exon/intron boundaries of two genes (CLDN16 and FGF12) in this interval did not reveal disease-causing mutations.
