TY - JOUR
T1 - Homozygosity mapping places the acrodermatitis enteropathica gene on chromosomal region 8q24.3
AU - Wang, K.
AU - Pugh, E. W.
AU - Griffen, S.
AU - Doheny, K. F.
AU - Mostafa, W. Z.
AU - Al-Aboosi, M. M.
AU - El-Shanti, H.
AU - Gitschier, J.
N1 - Funding Information:
We are indebted to the families that participated in this study. K.W. is grateful to Bing Zhou for stimulating discussions and to Anjali Shah for help with genotyping. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through federal contract N01-HG-65403 from the National Institutes of Health to the Johns Hopkins University. J.G. is an investigator for, and K.W. is an associate of, the Howard Hughes Medical Institute.
PY - 2001
Y1 - 2001
N2 - Acrodermatitis enteropathica (AE) is a rare autosomal recessive pediatric disease characterized by dermatitis, diarrhea, alopecia, and growth failure. The disease results from insufficient uptake of zinc by the intestine and can be fatal unless the diet is supplemented with zinc. To map the gene responsible for AE, a genomewide screen was performed on 17 individuals, including 4 affected individuals, in a consanguineous Jordanian family. Three markers - D8S373, D10S212, and D6S1021 - had a pattern consistent with tight linkage to a recessive disease: one allele in the affected sibs and multiple alleles in unaffected sibs and parents. Two-point parametric linkage analysis using FASTLINK identified one region, D8S373, with a maximum LOD score >1.5 (1.94 at D8S373: recombination fraction .001). Twelve additional markers flanking D8S373 were used to genotype the extended family, to fine-map the AE gene. All five affected individuals - including one who was not genotyped in the genomewide screen - were found to be homozygous for a common haplotype, spanning ∼3.5 cM, defined by markers D8S1713 and D8S2334 on chromosomal region 8q24.3. To support these mapping data, seven consanguineous Egyptian families with eight patients with AE were genotyped using these markers, and six patients from five families were found to be homozygous in this region. Multipoint analysis with all consanguineous families, by Mapmaker/Homoz, resulted in a maximum LOD score of 3.89 between D8S1713 and D8S373. Sliding three-point analysis resulted in a maximum LOD score of 5.16 between markers D8S1727 and D8S1744.
AB - Acrodermatitis enteropathica (AE) is a rare autosomal recessive pediatric disease characterized by dermatitis, diarrhea, alopecia, and growth failure. The disease results from insufficient uptake of zinc by the intestine and can be fatal unless the diet is supplemented with zinc. To map the gene responsible for AE, a genomewide screen was performed on 17 individuals, including 4 affected individuals, in a consanguineous Jordanian family. Three markers - D8S373, D10S212, and D6S1021 - had a pattern consistent with tight linkage to a recessive disease: one allele in the affected sibs and multiple alleles in unaffected sibs and parents. Two-point parametric linkage analysis using FASTLINK identified one region, D8S373, with a maximum LOD score >1.5 (1.94 at D8S373: recombination fraction .001). Twelve additional markers flanking D8S373 were used to genotype the extended family, to fine-map the AE gene. All five affected individuals - including one who was not genotyped in the genomewide screen - were found to be homozygous for a common haplotype, spanning ∼3.5 cM, defined by markers D8S1713 and D8S2334 on chromosomal region 8q24.3. To support these mapping data, seven consanguineous Egyptian families with eight patients with AE were genotyped using these markers, and six patients from five families were found to be homozygous in this region. Multipoint analysis with all consanguineous families, by Mapmaker/Homoz, resulted in a maximum LOD score of 3.89 between D8S1713 and D8S373. Sliding three-point analysis resulted in a maximum LOD score of 5.16 between markers D8S1727 and D8S1744.
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U2 - 10.1086/319514
DO - 10.1086/319514
M3 - Article
C2 - 11254458
AN - SCOPUS:0035074296
SN - 0002-9297
VL - 68
SP - 1055
EP - 1060
JO - American journal of human genetics
JF - American journal of human genetics
IS - 4
ER -