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

摘要: 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 a homozygous state two siblings diagnosed with PLS consanguineous family of Arabic ancestry. The variant initially heterozygous unaffected sibling whose whole exome had been sequenced as part previous Primary ciliary dyskinesia study. Using this information, proxy molecular diagnosis made on affected after consent given to study second found be segregating within family. prevalence then assayed local population using representative sample 256 unrelated individuals. absent all subjects indicating that rare Saudi Arabia. This illustrates how whole-exome sequencing can generate findings inferences beyond its primary goal.