Proxy Molecular Diagnosis from Whole-Exome Sequencing Reveals Papillon-Lefevre Syndrome Caused by a Missense Mutation in CTSC

A. Mesut Erzurumluoglu, Santiago Rodriguez, Philip A I Guthrie, Ian N M Day, Tom R Gaunt

Research output: Contribution to journalArticle (Academic Journal)peer-review

4 Citations (Scopus)
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Abstract

Papillon-Lefevre syndrome (PLS) is an autosomal recessive disorder characterised by severe early onset periodontitis and palmoplantar hyperkeratosis. A previously reported missense mutation in the CTSC gene (NM_001814.4:c.899G>A:p.(G300D)) was identified in a homozygous state in two siblings diagnosed with PLS in a consanguineous family of Arabic ancestry. The variant was initially identified in a heterozygous state in a PLS unaffected sibling whose whole exome had been sequenced as part of a previous Primary ciliary dyskinesia study. Using this information, a proxy molecular diagnosis was made on the PLS affected siblings after consent was given to study this second disorder found to be segregating within the family. The prevalence of the mutation was then assayed in the local population using a representative sample of 256 unrelated individuals. The variant was absent in all subjects indicating that the variant is rare in Saudi Arabia. This family study illustrates how whole-exome sequencing can generate findings and inferences beyond its primary goal.
Original languageEnglish
Article numbere0121351
Number of pages8
JournalPLoS ONE
Volume10
Issue number3
DOIs
Publication statusPublished - 23 Mar 2015

Keywords

  • whole-exome sequencing
  • papillon-lefevre syndrome
  • proxy molecular diagnosis
  • primary ciliary dyskinesia
  • CTSC
  • Next generation sequencing
  • Genetics

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