Refined mapping of X-linked reticulate pigmentary disorder and sequencing of candidate genes

Lane J. Jaeckle Santos, Chao Xing, Robert B. Barnes, Lesley C. Ades, Andre Megarbane, Christopher Vidal, Angela Xuereb, Patrick S. Tarpey, Raffaella Smith, Mahmoud Khazab, Cheryl Shoubridge, Michael Partington, Andrew Futreal, Michael R. Stratton, Jozef Gecz, Andrew R. Zinn

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 ∼ 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.

Original languageEnglish (US)
Pages (from-to)469-476
Number of pages8
JournalHuman Genetics
Volume123
Issue number5
DOIs
StatePublished - Jun 2008

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Exons
Genetic Linkage
Genes
X-Linked Genes
Mutation
Pedigree
Microsatellite Repeats
Inflammation
Polymerase Chain Reaction
Skin
Population
Pigmentary Disorder, Reticulate, with Systemic Manifestations

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Refined mapping of X-linked reticulate pigmentary disorder and sequencing of candidate genes. / Jaeckle Santos, Lane J.; Xing, Chao; Barnes, Robert B.; Ades, Lesley C.; Megarbane, Andre; Vidal, Christopher; Xuereb, Angela; Tarpey, Patrick S.; Smith, Raffaella; Khazab, Mahmoud; Shoubridge, Cheryl; Partington, Michael; Futreal, Andrew; Stratton, Michael R.; Gecz, Jozef; Zinn, Andrew R.

In: Human Genetics, Vol. 123, No. 5, 06.2008, p. 469-476.

Research output: Contribution to journalArticle

Jaeckle Santos, LJ, Xing, C, Barnes, RB, Ades, LC, Megarbane, A, Vidal, C, Xuereb, A, Tarpey, PS, Smith, R, Khazab, M, Shoubridge, C, Partington, M, Futreal, A, Stratton, MR, Gecz, J & Zinn, AR 2008, 'Refined mapping of X-linked reticulate pigmentary disorder and sequencing of candidate genes', Human Genetics, vol. 123, no. 5, pp. 469-476. https://doi.org/10.1007/s00439-008-0498-4
Jaeckle Santos, Lane J. ; Xing, Chao ; Barnes, Robert B. ; Ades, Lesley C. ; Megarbane, Andre ; Vidal, Christopher ; Xuereb, Angela ; Tarpey, Patrick S. ; Smith, Raffaella ; Khazab, Mahmoud ; Shoubridge, Cheryl ; Partington, Michael ; Futreal, Andrew ; Stratton, Michael R. ; Gecz, Jozef ; Zinn, Andrew R. / Refined mapping of X-linked reticulate pigmentary disorder and sequencing of candidate genes. In: Human Genetics. 2008 ; Vol. 123, No. 5. pp. 469-476.
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