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PLoS One. 2015 Mar 23;10(3):e0121351. doi: 10.1371/journal.pone.0121351. eCollection 2015.

Proxy molecular diagnosis from whole-exome sequencing reveals Papillon-Lefevre syndrome caused by a missense mutation in CTSC.

Author information

1
Bristol Genetic Epidemiology Laboratories (BGEL), University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom.
2
College of Medicine, Pediatric Department, King Saud University, P.O. Box 50807, Riyadh, 11533, Kingdom of Saudi Arabia.
3
Bristol Genetic Epidemiology Laboratories (BGEL), University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom; MRC Integrative Epidemiology Unit (IEU), School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom.
4
Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433, Kingdom of Saudi Arabia.
5
Department of Dermatology, King Saud University, P.O. Box 7805, Riyadh, 11472, Kingdom of Saudi Arabia.

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.

PMID:
25799584
PMCID:
PMC4370501
DOI:
10.1371/journal.pone.0121351
[Indexed for MEDLINE]
Free PMC Article

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