A novel locus for dHMN with pyramidal features maps to chromosome 4q34.3-q35.2

• Published in: Clinical genetics 2008-05, Vol.73 (5), p.486-491
• Main Authors: Muglia, M, Magariello, A, Citrigno, L, Passamonti, L, Sprovieri, T, Conforti, FL, Mazzei, R, Patitucci, A, Gabriele, AL, Ungaro, C, Bellesi, M, Quattrone, A
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; candidate genes; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 4 - genetics; Classical genetics, quantitative genetics, hybrids; distal motor neuropathy; Female; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetic disorders; Genetic Heterogeneity; Genetic Linkage; Genetic markers; Genetics of eukaryotes. Biological and molecular evolution; Hereditary Sensory and Motor Neuropathy - genetics; Hereditary Sensory and Motor Neuropathy - physiopathology; Human; Humans; linkage analysis; Male; Medical genetics; Medical sciences; Molecular and cellular biology; Muscular system; Mutation; Neurosciences; Pedigree
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2008.00969.x

The distal hereditary motor neuropathy (dHMN) is a rare genetically and clinically heterogeneous disorder characterized by weakness and wasting of distal limb muscles in absence of overt sensory abnormalities. Recently, pyramidal signs have been also described in some patients with dominant or recessive dHMN, and two different loci have been identified in families affected by dHMN complicated with pyramidal dysfunction. We investigated an Italian family affected by an autosomal dominant dHMN complicated by pyramidal signs in order to map a new gene locus. The disease maps to a novel locus in a 26‐cM region flanked by D4S1552 and D4S2930 on chromosome 4q34.3‐35.2. Three candidate genes (SNX25, CASP3 and TUBB4Q) located in the critical region were screened for the presence of mutations by heteroduplex analysis. No mutations have been detected in the analyzed genes. In conclusion, the new private genetic locus we reported further confirms the wide heterogeneity of dHMN.