Homozygosity mapping of a locus for a novel syndromic ichthyosis to chromosome 3q27-q28.
Ichthyosis is a heterogeneous group of skin disorders characterized by abnormal epidermal scaling. Occasionally, extracutaneous features are associated. A novel autosomal recessive ichthyosis syndrome is described here with scalp hypotrichosis, scarring alopecia, sclerosing cholangitis, and leukocyte vacuolization in two inbred kindreds of Moroccan origin. We also report the mapping of the diseased gene to a 21.2 cM interval of chromosome 3q27-q28. Homo zygosity for polymorphic markers has enabled us to reduce the genetic interval to a 16.2 cM region. Furthermore, comparison of mutant chromosomes in the two families has suggested a common ancestral mutant haplotype. This linkage disequilibrium has reduced the genetic interval encompassing the diseased gene to less than 9.5 cM maximum. Further study of additional families from the same geographic area will hopefully reduce the genetic interval as well as help in the cloning of the gene involved in this rare disorder.
Baala
Lekbir
L
Département de Génétique et Unité de Recherches sur les Handicaps Génétiques de l'Enfant INSERM U-393, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France.
Hadj-Rabia
Smaïl
S
Hamel-Teillac
Dominique
D
Hadchouel
Michelle
M
Prost
Catherine
C
Leal
Suzanne M
SM
Jacquemin
Emmanuel
E
Sefiani
Abdelaziz
A
De Prost
Yves
Y
Courtois
Gilles
G
Munnich
Arnold
A
Lyonnet
Stanislas
S
Vabres
Pierre
P
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015209:Cholangitis, Sclerosing / Q000235:genetics / Q000473:pathology; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D003241:Consanguinity; D005192:Family Health; D005260:Female; D018703:Founder Effect; D006720:Homozygote; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics / Q000473:pathology; D007057:Ichthyosis / Q000235:genetics* / Q000473:pathology; D015603:Keratinocytes / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D008297:Male; D009018:Morocco; D010375:Pedigree; D012535:Scalp