title: Terminal osseous dysplasia with pigmentary defects maps to human chromosome Xq27.3-xqter.
abstract: We have identified a four-generation family with 10 affected females manifesting one or more of the following features: osseous dysplasia involving the metacarpals, metatarsals, and phalanges leading to brachydactyly, camptodactyly, and other digital deformities; pigmentary defects on the face and scalp; and multiple frenula. There were no affected males. We performed X-inactivation studies on seven affected females, using a methylation assay at the androgen receptor locus; all seven demonstrated preferential inactivation of their maternal chromosomes carrying the mutation, and two unaffected females showed a random pattern. These findings indicate that this disorder is linked to the X chromosome. To map the gene for this disorder, we analyzed DNA from nine affected females and five unaffected individuals, using 40 polymorphic markers evenly distributed throughout the X chromosome. Two-point and multipoint linkage analyses using informative markers excluded most of the X chromosome and demonstrated linkage to a region on the long arm between DXS548 and Xqter. A maximum LOD score of 3.16 at recombination fraction 0 was obtained for five markers mapping to Xq27.3-Xq28. The mapping data should facilitate the identification of the molecular basis of this disorder.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Amir
authors.forename: D W
authors.initials: DW
authors.lastname: Stockton
authors.forename: I B
authors.initials: IB
authors.lastname: Van Den Veyver
authors.forename: C A
authors.initials: CA
authors.lastname: Bacino
authors.forename: H Y
authors.initials: HY
authors.lastname: Zoghbi
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D001848:Bone Diseases, Developmental / Q000235:genetics*; D002874:Chromosome Mapping; D019175:DNA Methylation; D004303:Dosage Compensation, Genetic; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008126:Lod Score; D008297:Male; D010375:Pedigree; D010859:Pigmentation Disorders / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011995:Recombination, Genetic; D014960:X Chromosome / Q000235:genetics*