Logo image
Back
Expanding the genetic and phenotypic spectrum of popliteal pterygium disorders
Journal article   Open access   Peer reviewed

Expanding the genetic and phenotypic spectrum of popliteal pterygium disorders

Elizabeth J Leslie, James O'Sullivan, Michael L Cunningham, Ankur Singh, Steven L Goudy, Faroug Ababneh, Lamia Alsubaie, Gaik-Siew Ch'ng, Ingrid M B H van der Laar, A Jeannette M Hoogeboom, …
American journal of medical genetics. Part A, Vol.167A(3), pp.545-552
03/2015
DOI: 10.1002/ajmg.a.36896
PMCID: PMC4423539
PMID: 25691407

View Online

Abstract

The popliteal pterygia syndromes are a distinct subset of the hundreds of Mendelian orofacial clefting syndromes. Popliteal pterygia syndromes have considerable variability in severity and in the associated phenotypic features but are all characterized by cutaneous webbing across one or more major joints, cleft lip and/or palate, syndactyly, and genital malformations. Heterozygous mutations in IRF6 cause popliteal pterygium syndrome (PPS) while homozygous mutations in RIPK4 or CHUK (IKKA) cause the more severe Bartsocas-Papas syndrome (BPS) and Cocoon syndrome, respectively. In this study, we report mutations in six pedigrees with children affected with PPS or BPS. Using a combination of Sanger and exome sequencing, we report the first case of an autosomal recessive popliteal pterygium syndrome caused by homozygous mutation of IRF6 and the first case of uniparental disomy of chromosome 21 leading to a recessive disorder. We also demonstrate that mutations in RIPK4 can cause features with a range of severity along the PPS-BPS spectrum and that mutations in IKKA can cause a range of features along the BPS-Cocoon spectrum. Our findings have clinical implications for genetic counseling of families with pterygia syndromes and further implicate IRF6, RIPK4, and CHUK (IKKA) in potentially interconnected pathways governing epidermal and craniofacial development.
 Mutation Phenotype Cleft Palate - diagnosis Cleft Lip - diagnosis Humans Knee - abnormalities Infant Male Cleft Palate - genetics Exome DNA Mutational Analysis Female Fingers - abnormalities Lower Extremity Deformities, Congenital - genetics Infant, Newborn Eye Abnormalities - diagnosis Genome-Wide Association Study Genetic Association Studies Urogenital Abnormalities - diagnosis Protein-Serine-Threonine Kinases - genetics Interferon Regulatory Factors - genetics Lower Extremity Deformities, Congenital - diagnosis I-kappa B Kinase - genetics Eye Abnormalities - genetics Genes, Recessive Cleft Lip - genetics Comparative Genomic Hybridization Pedigree Knee Joint - abnormalities High-Throughput Nucleotide Sequencing Syndactyly - diagnosis Syndactyly - genetics Urogenital Abnormalities - genetics

Details

Metrics

43 Record Views
37 Times Cited - Web of Science
Logo image