Two new loci for autosomal recessive ichthyosis on chromosomes 3p21 and 19p12-q12 and evidence for further genetic heterogeneity - PubMed (original) (raw)

Two new loci for autosomal recessive ichthyosis on chromosomes 3p21 and 19p12-q12 and evidence for further genetic heterogeneity

J Fischer et al. Am J Hum Genet. 2000 Mar.

Abstract

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.

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Figures

Figure 1

Figure 1

Pedigrees of six consanguineous nuclear LI families with linkage to chromosome 19. Haplotypes for 29 microsatellite markers from chromosome 19p12-q12 are shown. Affected individuals are indicated by blackened symbols, and the homozygous region that segregates with the disease phenotype is circled.

Figure 2

Figure 2

Pedigrees of six consanguineous nuclear NCIE families with linkage to chromosome 3. Haplotypes for 33 microsatellite markers from chromosome 3p21 are shown. Affected individuals are indicated by blackened symbols, and the homozygous region that segregates with the disease phenotype is circled.

Figure 3

Figure 3

Limits of the common interval (shaded) in the chromosome 19–linked LI families.

Figure 4

Figure 4

Limits of the common interval (shaded) in the chromosome 3–linked NCIE families.

References

Electronic-Database Information

    1. Human Gene Map (NCBI), http:/www.ncbi.nlm.nih.gov/SCIENCE96/ (for expressed sequence tags within the critical interval between D3S3522 and D3S1581, and D19S899 and D19S405)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim (for lamellar ichthyosis [MIM 242300, MIM 601277], nonbullous ichthyosiform erythroderma [MIM 242100], Sjögren-Larsson syndrome [MIM 270200], Refsum syndrome [MIM 266500], autosomal dominant ichthyosis vulgaris [MIM 146700], autosomal dominant lamellar ichthyosis [MIM 146750], XLRI [MIM 308100], TGM1 [MIM 190195], FALDH [MIM 100660], PHYH [MIM 602026], TGM4 [MIM 600585], ACAA1 [MIM 604054], CYP8B1 [MIM 602172], LAMR1 [MIM 150370], COL7A1 [MIM 120120], PTGER1 [MIM 176802], UQCRC1 [MIM 191328], UQCRFS1 [MIM 191327], MAP4 [MIM 157132], MAP2 [MIM 157130])

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