title: A Novel Locus for Ectodermal Dysplasia of Hair, Nail and Skin Pigmentation Anomalies Maps to Chromosome 18p11.32-p11.31.
abstract: Ectodermal dysplasias (EDs) are a large heterogeneous group of inherited disorders exhibiting abnormalities in ectodermally derived appendages such as hair, nails, teeth and sweat glands. EDs associated with reticulated pigmentation phenotype are rare entities for which the genetic basis and pathophysiology are not well characterized. The present study describes a five generation consanguineous Pakistani family segregating an autosomal recessive form of a novel type of ectodermal dysplasia. The affected members present with sparse and woolly hair, severe nail dystrophy and reticulate skin pigmentation. After exclusion of known gene loci related with other skin disorders, genome-wide linkage analysis was performed using Illumina HumanOmniExpress beadchip SNP arrays. We linked this form of ED to human chromosome 18p11.32-p11.31 flanked by the SNPs rs9284390 (0.113Mb) and rs4797100 (3.14 Mb). A maximum two-point LOD score of 3.3 was obtained with several markers along the disease interval. The linkage interval of 3.03 Mb encompassed seventeen functional genes. However, sequence analysis of all these genes did not discover any potentially disease causing-variants. The identification of this novel locus provides additional information regarding the mapping of a rare form of ED. Further research, such as the use of whole-genome sequencing, would be expected to reveal any pathogenic mutation within the disease locus.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Rabia
authors.initials: R
authors.lastname: Habib
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ansar
authors.affiliation: Department of Genomic Mathematics, University of Bonn, Bonn, Germany; Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mattheisen
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Shahid
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Ghazanfar
authors.initials: G
authors.lastname: Ali
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Regina C
authors.initials: RC
authors.lastname: Betz
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004476:Ectodermal Dysplasia / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006197:Hair / Q000002:abnormalities; D006801:Humans; D008126:Lod Score; D008297:Male; D009264:Nails, Malformed / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D040641:Quantitative Trait Loci; D012868:Skin Abnormalities / Q000235:genetics; D012880:Skin Pigmentation / Q000235:genetics; D055815:Young Adult