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Identification, by homozygosity mapping, of a novel locus for autosomal recessive congenital ichthyosis on chromosome 17p, and evidence for further genetic heterogeneity

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Creators Name:Krebsova, A. and Kuester, W. and Lestringant, G.G. and Schulze, B. and Hinz, B. and Frossard, P.M. and Reis, A. and Hennies, H.C.
Journal Title:American Journal of Human Genetics
Journal Abbreviation:Am J Hum Genet
Page Range:216-222
Date:1 January 2001
Keywords:Chromosome Mapping, Consanguinity, Genetic Heterogeneity, Genetic Markers, Germany, Haplotypes, Ichthyosis, Lod Score, Pair 17 Human Chromosomes, Recessive Genes, Turkey, United Arab Emirates
Abstract:Autosomal recessive congenital ichthyosis (ARCI) comprises a group of severe disorders of keratinization, characterized by variable erythema and skin scaling. It is known for its high degree of genetic and clinical heterogeneity. Mutations in the gene for keratinocyte transglutaminase (TGM1) on chromosome 14q11 were shown in patients with ARCI, and a second locus was described, on chromosome 2q, in families from northern Africa. Three other loci for ARCI, on chromosomes 3p and 19p, were identified recently. We have embarked on a whole-genome scan for further loci for ARCI in four families from Germany, Turkey, and the United Arab Emirates. A novel ARCI locus was identified on chromosome 17p, between the markers at D17S938 and D17S1856, with a maximum LOD score of 3.38, at maximum recombination fraction 0.00, at D17S945, under heterogeneity. This locus is linked to the disease in the Turkish family and in the German family. Extensive genealogical studies revealed that the parents of the German patients with ARCI were eighth cousins. By homozygosity mapping, the localization of the gene could then be refined to the 8.4-cM interval between D17S938 and D17S1879. It could be shown, however, that ARCI in the two Arab families is linked neither to the new locus on chromosome 17p nor to one of the five loci known previously. Our findings give evidence of further genetic heterogeneity that is not linked to distinctive phenotypes.
Publisher:University of Chicago Press (U.S.A.)
Item Type:Article

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