Two New Loci for Autosomal Recessive Ichthyosis on Chromosomes 3p21 and 19p12-q12 and Evidence for Further Genetic Heterogeneity

• Published in: American journal of human genetics 2000-03, Vol.66 (3), p.904-913
• Main Authors: Fischer, Judith, Faure, Alexandra, Bouadjar, Bakar, Blanchet-Bardon, Claudine, Karaduman, Aysen, Thomas, Isabelle, Emre, Serap, Cure, Susan, Özgüc, Meral, Weissenbach, Jean, Prud'homme, Jean-François
• Format: Article
• Language: English
• Subjects: Biochemistry, Molecular Biology; Biological and medical sciences; Chromosome 19; Chromosome 3; Chromosome Mapping; Chromosomes, Human, Pair 19 - genetics; Chromosomes, Human, Pair 3 - genetics; Consanguinity; Dermatology; Female; Genes, Recessive - genetics; Genetic Heterogeneity; Genetic Markers - genetics; Genomics; Haplotypes - genetics; Hereditary diseases of the skin. Congenital diseases of the skin. Haemangioma of the skin, of mucosae and of soft tissue; Homozygosity mapping; Homozygote; Humans; Ichthyosiform Erythroderma, Congenital - genetics; Ichthyosiform Erythroderma, Congenital - pathology; Ichthyosis - genetics; Ichthyosis - pathology; Ichthyosis, autosomal recessive; Lamellar ichthyosis; Life Sciences; Lod Score; Male; Medical sciences; Mediterranean Region; Nonbullous congenital ichthyosiform erythroderma; Pedigree; Tropical medicine
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/302814

Autosomal recessive ichthyosis (ARI) includes a heterogeneous group of disorders of keratinization characterized by desquamation over the whole body. Two forms largely limited to the skin have been defined: lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE). A first gene for LI, transglutaminase TGM1, has been identified on chromosome 14, and a second one has been localized on chromosome 2. In a genomewide scan of nine large consanguineous families, using homozygosity mapping, two new loci for ARI were found, one for a lamellar form in a 6-cM interval on chromosome 19 and a second for an erythrodermic form in a 7.7-cM interval on chromosome 3. Linkage to one of the four loci could be demonstrated in more than half of 51 consanguineous families, most of them from the Mediterranean basin. All four loci could be excluded in the others, implying further genetic heterogeneity in this disorder. Multipoint linkage analysis gave maximal LOD scores of 11.25 at locus D19S566 and 8.53 at locus D3S3564.