Genetic Heterogeneity of Hereditary Sensory Neuropathy

Abstract

Hereditary sensory neuropathy has been considered a dominant trait, but a recessive transmission has been suggested in a few reports. The segregation ratio in those sibships having normal parents was 0.26, and the rate of parental consanguinity was greatly elevated. In sibships with one affected parent, the ratio was 0.50 for the boys but less for the girls, and the parents were unrelated. These findings indicate that recessive inheritance is applicable in the former group, while cases in the latter group are inherited dominantly with a reduced penetrance in the female homozygotes. Age of onset was younger in recessive cases, but other clinical features appeared identical in both groups.

Mutations in the nervous system–specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II

“…Rouleau's group in Montreal by L. Faivre for an HSN2 genetic analysis to confirm the diagnosis of HSANII in an 18-year-old female. Clinically, she had classic HSANII symptoms (2)(3)(4). Examination of the patient revealed no dysautonomia or abnormal blood pressure.…”

“…Hereditary sensory and autonomic neuropathy type II (HSANII; OMIM 201300) is an early-onset autosomal recessive disorder. It is characterized by loss of perception to pain, touch, and heat attributable to a partial loss of peripheral sensory nerves (2)(3)(4). In 2004, we reported mutations in the hereditary sensory neuropathy type II (HSN2) gene, a single-exon ORF identified in Quebec and Newfoundland families, as the cause of HSANII (5).…”

HSANs: Clinical Features, Pathologic Classification, and Molecular Genetics

“…A homozygous insertional mutation (918-919insA) was found in the Nova Scotia family leading to a truncation of the protein to 318 amino acids. Previously, we 40,50,132 and others 106 have suggested that congenital sensory neuropathy might be recessively inherited and a separate disorder(s) from dominantly inherited sensory neuropathy. Such mutations were not found in a large cohort of appropriate normal controls.…”

Novel mutation in the HSN2 gene in a Korean patient with hereditary sensory and autonomic neuropathy type 2

“…The autosomal recessive disorder HSAN2 results from segmental demyelination and the loss of axons in the peripheral nervous system (Kondo and Horikawa 1974;Murray 1973). Although the function of HSN2 protein remains to be determined, the identification of diseaseassociated mutations would provide considerable insight into the structural and function of HSN2 protein.…”

“…Among these, HSAN type 2 (HSAN2; MIM 201300) is a rare recessive disease that was first clearly described in 1973 (Ota et al 1973). HSAN2 is characterized by an early age of onset with distal and proximal sensory loss, dysfunction of the autonomic nervous system, loss of the tendon reflex, the presence of various mutilation and the slow progression of the disease over time (Kondo and Horikawa 1974;Murray 1973). Mutations in a novel gene named HSN2 at 12p13.33 have been identified as being the cause of HSAN2 in Canadian and Lebanese patients Riviere et al 2004;Roddier et al 2005).…”