A locus for hereditary sensory neuropathy with cough and gastroesophageal reflux on chromosome 3p22-p24

Abstract

Hereditary sensory neuropathy type I (HSN I) is a group of dominantly inherited degenerative disorders of peripheral nerve in which sensory features are more prominent than motor involvement. We have described a new form of HSN I that is associated with cough and gastroesophageal reflux. To map the chromosomal location of the gene causing the disorder, a 10-cM genome screen was undertaken in a large Australian family. Two-point analysis showed linkage to chromosome 3p22-p24 (Zmax=3.51 at recombination fraction (theta) 0.0 for marker D3S2338). A second family with a similar phenotype shares a different disease haplotype but segregates at the same locus. Extended haplotype analysis has refined the region to a 3.42-cM interval, flanked by markers D3S2336 and D3S1266.

Figure 1

Genetic map (sex averaged) of chromosome 3 markers used in the present study. The marker-map positions are based on the sex-averaged maps from the Center for Medical Genetics, Marshfield Medical Research Foundation. Loci on the same line were mapped to the same genetic location. Markers flanking the HSN I with cough and GER genetic interval are shown in boldface.

Figure 2

Haplotype analysis of markers from chromosome 3p22-p24 in families HSN32 and HSN35 with autosomal dominant HSN I with cough and GER. The haplotype segregating with the disease is indicated (blackened bar). The markers are presented in order from telomere (top) to centromere (bottom). Blackened symbols denote affected individuals; unblackened symbols denote unaffected individuals; individuals with unknown clinical status are denoted by a question mark. Individuals are numbered consecutively in each generation, from left to right. Individual III:5 in family HSN35 defines the telomeric boundary of the disease at D3S2336, whereas individual III:9 in family HSN32 defines the centromeric boundary at D3S1266.