A syndromic form of Pierre Robin sequence is caused by 5q23 deletions encompassing FBN2 and PHAX

Morad Ansari, Jacqueline K Rainger, Jennie E Murray, Isabel Hanson, Helen V Firth, Felicity Mehendale, Jeanne Amiel, Christopher T Gordon, Antonio Percesepe, Laura Mazzanti, Alan Fryer, Paola Ferrari, Koenraad Devriendt, I Karen Temple, David R FitzPatrick

Research output: Contribution to journalArticlepeer-review


Pierre Robin sequence (PRS) is an aetiologically distinct subgroup of cleft palate. We aimed to define the critical genomic interval from five different 5q22-5q31 deletions associated with PRS or PRS-associated features and assess each gene within the region as a candidate for the PRS component of the phenotype. Clinical array-based comparative genome hybridisation (aCGH) data were used to define a 2.08 Mb minimum region of overlap among four de novo deletions and one mother-son inherited deletion associated with at least one component of PRS. Commonly associated anomalies were talipes equinovarus (TEV), finger contractures and crumpled ear helices. Expression analysis of the orthologous genes within the PRS critical region in embryonic mice showed that the strongest candidate genes were FBN2 and PHAX. Targeted aCGH of the critical region and sequencing of these genes in a cohort of 25 PRS patients revealed no plausible disease-causing mutations. In conclusion, deletion of ∼2 Mb on 5q23 region causes a clinically recognisable subtype of PRS. Haploinsufficiency for FBN2 accounts for the digital and auricular features. A possible critical region for TEV is distinct and telomeric to the PRS region. The molecular basis of PRS in these cases remains undetermined but haploinsufficiency for PHAX is a plausible mechanism.

Original languageEnglish
Pages (from-to)587-95
Number of pages9
JournalEuropean journal of medical genetics
Issue number10
Publication statusPublished - Oct 2014


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