Resolving clinical diagnoses for syndromic cleft lip and/or palate phenotypes using whole-exome sequencing

摘要: Individuals from three families ascertained in Bogota, Colombia, showing syndromic phenotypes, including cleft lip and/or palate, were exome sequenced. In each case sequencing revealed underlying causal variation confirming or establishing diagnoses. The findings include very rare and novel variants providing insights into genotype phenotype relationships. These the molecular diagnosis of an individual with Nager syndrome a family exhibiting atypical Incontinentia Pigmenti missense mutation IKBKG. IKBKG mutations are typically associated pre-term male death but this variant is survival for 8–15 days. third exhibits unusual phenotypic features proband received provisional Pierre Robin Sequence (PRS). Affected individuals share deleterious IRF6. Mutations IRF6 cause Van der Woude Popliteal pterygium contribute to nonsyndromic phenotypes have not previously been PRS phenotype. Exome followed by silico screening identify candidate variant(s), functional assay some cases, offers powerful route This approach invaluable conditions genetic heterogeneity palate where many genes identified.