title: Copy-number mutations on chromosome 17q24.2-q24.3 in congenital generalized hypertrichosis terminalis with or without gingival hyperplasia.
abstract: Congenital generalized hypertrichosis terminalis (CGHT) is a rare condition characterized by universal excessive growth of pigmented terminal hairs and often accompanied with gingival hyperplasia. In the present study, we describe three Han Chinese families with autosomal-dominant CGHT and a sporadic case with extreme CGHT and gingival hyperplasia. We first did a genome-wide linkage scan in a large four-generation family. Our parametric multipoint linkage analysis revealed a genetic locus for CGHT on chromosome 17q24.2-q24.3. Further two-point linkage and haplotyping with microsatellite markers from the same chromosome region confirmed the genetic mapping and showed in all the families a microdeletion within the critical region that was present in all affected individuals but not in unaffected family members. We then carried out copy-number analysis with the Affymetrix Genome-Wide Human SNP Array 6.0 and detected genomic microdeletions of different sizes and with different breakpoints in the three families. We validated these microdeletions by real-time quantitative PCR and confirmed their perfect cosegregation with the disease phenotype in the three families. In the sporadic case, however, we found a de novo microduplication. Two-color interphase FISH analysis demonstrated that the duplication was inverted. These copy-number variations (CNVs) shared a common genomic region in which CNV is not reported in the public database and was not detected in our 434 unrelated Han Chinese normal controls. Thus, pathogenic copy-number mutations on 17q24.2-q24.3 are responsible for CGHT with or without gingival hyperplasia. Our work identifies CGHT as a genomic disorder.
authors.affiliation: McKusick-Zhang Center for Genetic Medicine and State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Wu
authors.initials: W
authors.lastname: Dong
authors.forename: Zugen
authors.initials: Z
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Yiming
authors.initials: Y
authors.lastname: Xu
authors.forename: Guang
authors.initials: G
authors.lastname: He
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Shi
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Jiajie
authors.initials: J
authors.lastname: Hao
authors.forename: Yang
authors.initials: Y
authors.lastname: Luo
authors.forename: Dandan
authors.initials: D
authors.lastname: Shang
authors.forename: Dan
authors.initials: D
authors.lastname: Lv
authors.forename: Fen
authors.initials: F
authors.lastname: Ma
authors.forename: Dai
authors.initials: D
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Hua
authors.forename: Chaoxia
authors.initials: C
authors.lastname: Lu
authors.forename: Yaran
authors.initials: Y
authors.lastname: Wen
authors.forename: Lihua
authors.initials: L
authors.lastname: Cao
authors.forename: Alan D
authors.initials: AD
authors.lastname: Irvine
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.forename: Qi
authors.initials: Q
authors.lastname: Dong
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Wilson H Y
authors.initials: WH
authors.lastname: Lo
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D008040:Genetic Linkage; D015894:Genome, Human; D005885:Gingival Hyperplasia / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006983:Hypertrichosis / Q000151:congenital* / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D055758:SOX9 Transcription Factor / Q000235:genetics
chemical_list: D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human