title: Refined mapping of X-linked reticulate pigmentary disorder and sequencing of candidate genes.
abstract: X-linked reticulate pigmentary disorder with systemic manifestations in males (PDR) is very rare. Affected males are characterized by cutaneous and visceral symptoms suggestive of abnormally regulated inflammation. A genetic linkage study of a large Canadian kindred previously mapped the PDR gene to a greater than 40 Mb interval of Xp22-p21. The aim of this study was to identify the causative gene for PDR. The Canadian pedigree was expanded and additional PDR families recruited. Genetic linkage was performed using newer microsatellite markers. Positional and functional candidate genes were screened by PCR and sequencing of coding exons in affected males. The location of the PDR gene was narrowed to a approximately 4.9 Mb interval of Xp22.11-p21.3 between markers DXS1052 and DXS1061. All annotated coding exons within this interval were sequenced in one affected male from each of the three multiplex families as well as one singleton, but no causative mutation was identified. Sequencing of other X-linked genes outside of the linked interval also failed to identify the cause of PDR but revealed a novel nonsynonymous cSNP in the GRPR gene in the Maltese population. PDR is most likely due to a mutation within the linked interval not affecting currently annotated coding exons.
authors.affiliation: McDermott Center for Human Growth and Development, The University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75390-8591, USA. lane.jaeckle@utsouthwestern.edu
authors.forename: Lane J
authors.initials: LJ
authors.lastname: Jaeckle Santos
authors.forename: Chao
authors.initials: C
authors.lastname: Xing
authors.forename: Robert B
authors.initials: RB
authors.lastname: Barnes
authors.forename: Lesley C
authors.initials: LC
authors.lastname: Ades
authors.forename: Andre
authors.initials: A
authors.lastname: Megarbane
authors.forename: Christopher
authors.initials: C
authors.lastname: Vidal
authors.forename: Angela
authors.initials: A
authors.lastname: Xuereb
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Tarpey
authors.forename: Raffaella
authors.initials: R
authors.lastname: Smith
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Khazab
authors.forename: Cheryl
authors.initials: C
authors.lastname: Shoubridge
authors.forename: Michael
authors.initials: M
authors.lastname: Partington
authors.forename: Andrew
authors.initials: A
authors.lastname: Futreal
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
authors.forename: Jozef
authors.initials: J
authors.lastname: Gecz
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Zinn
mesh_terms: D002874:Chromosome Mapping; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008297:Male; D010375:Pedigree; D010859:Pigmentation Disorders / Q000235:genetics*; D017422:Sequence Analysis, DNA