Open AccessProxy Molecular Diagnosis from Whole-Exome Sequencing Reveals Papillon-Lefevre Syndrome Caused by a Missense Mutation in CTSC
Author(s) -
A. Mesut Erzurumluoglu,
Muslim M. Alsaadi,
Santiago Rodríguez,
Tahani S. Alotaibi,
Philip A. I. Guthrie,
Siân Lewis,
Aasiya Ginwalla,
Tom R. Gaunt,
Khalid Khalaf Alharbi,
Fahad Alsaif,
Basma M. Alsaadi,
Ian N.M. Day
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0121351
Subject(s) - exome sequencing , missense mutation , genetics , population , exome , mutation , consanguinity , biology , medicine , gene , environmental health
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.