An atypical form of erythrokeratodermia variabilis maps to chromosome 7q22.
Erythrokeratodermia variabilis 3 (Kamouraska type) or EKV3 is a newly described autosomal recessive disorder observed in patients from the Bas St-Laurent region of Quebec. It has similar skin lesions as observed for EKV, including congenital hyperkeratosis and red patches of variable sizes, shapes, and duration. EKV3 is also characterized by ichthyosis, sensorineural hearing loss, peripheral neuropathy, psychomotor retardation, congenital chronic diarrhea, and an elevation of very long chain fatty acids (VLCFAs). To map the disease locus, we performed candidate gene analysis and a genomewide scan to identify a common homozygous region in affected individuals from three non-consanguineous families. Mutations in connexin 31 (GJB3) and connexin 30.3 (GJB4), implicated in previous reports of EKV, and connexin 26 (GJB2), implicated in palmoplantar keratoderma, were unlikely given the lack of shared homozygous haplotypes in the regions surrounding these genes. The most promising region of common homozygosity observed in a 4,600 single-nucleotide polymorphism genome scan was further characterized by using microsatellites. A 6.8-Mb region on chromosome 7 between D7S2539 and rs727708 was found to be homozygous for the same haplotype in all affected individuals but not in the parents or an unaffected sibling. This region contains connexin 31.3 (GJE1), and although no mutation have been observed in the coding region of this gene, further analyses are required in order to exclude it. Identification of the gene responsible for this disorder will provide insights into the etiology of this multisystemic disorder.
Saba
Thomas G
TG
McGill University and Genome Quebec Innovation Centre, Montreal, QC, H3A 1A4, Canada.
Montpetit
Alexandre
A
Verner
Andrei
A
Rioux
Pierre
P
Hudson
Thomas J
TJ
Drouin
Régen
R
Drouin
Christian A
CA
D002897:Chromosomes, Human, Pair 7; D000072259:Connexin 26; D017630:Connexins; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D010523:Peripheral Nervous System Diseases / Q000235:genetics; D012873:Skin Diseases, Genetic / Q000235:genetics*
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26