De novo 2.3 Mb microdeletion of 1q32.2 involving the Van der Woude Syndrome locus

Abstract

BackgroundVan der Woude syndrome is the most common among syndromes which include cleft lip and/or cleft palate as one of the presentations. It is usually caused by mutations in the interferon regulatory factor 6 (IRF6) gene.Case presentationWe previously reported on a patient with suspected deletion of the IRF6 gene. Using the Affymetrix Human SNP 6.0 Array, the interstitial deletion has been confirmed and found to be approximately 2.327–2.334 Mb within the 1q32.2 region. Although several known genes were deleted, the patient has no other phenotype apart from the orofacial presentations typical of VWS. The same deletion was not present in either parent and his two siblings were also phenotypically normal.ConclusionsOther than IRF6, the genes which are deleted in this patient appear to be insensitive to copy number and haploinsufficiency. We compared the deletion in this patient with another case which was also mapped by high resolution array but had additional phenotypic features.

Novel IRF6 mutations in families with Van Der Woude syndrome and popliteal pterygium syndrome from sub‐Saharan Africa

“…; Tan et al. ).To date, about 300 mutations causing VWS and PPS have been reported in different populations across the world (Leslie et al. ) and these include missense, nonsense, and frameshift, microdeletions and splice‐site mutations.…”

A genome‐wide study of inherited deletions identified two regions associated with nonsyndromic isolated oral clefts

“…This microdeletion included the IRF6 gene, where multiple distinct point mutations and a few small deletions (ranging in size from a few base pairs up to 17 kb) account for most inherited Van der Woude syndromes, the most common autosomal dominant Mendelian malformation syndrome including oral clefts (Salahshourifar et al, ). The deletion identified by Tan et al () started in a known copy number variant site and extended into a large intron of the neighboring gene STY14 , but IRF6 remained the gene predicted to be causal in this case.…”

“…Osoegawa et al () also examined 104 nonsyndromic oral cleft patients with array‐CGH to identify two individuals with deletions: one CLP proband with a de novo 3.2 Mb deletion on chr6q25.1–25.2 and one CL proband with a 2.2 Mb deletion on chr10q26.11–26.13 transmitted from the mother (who also had a CL). Tan et al () identified a de novo deletion spanning 2.3 Mb of chr1q32 in a CLP proband with lip pits (fitting the clinical phenotype for Van der Woude syndrome, although there was no family history of oral clefts or lip pits). This microdeletion included the IRF6 gene, where multiple distinct point mutations and a few small deletions (ranging in size from a few base pairs up to 17 kb) account for most inherited Van der Woude syndromes, the most common autosomal dominant Mendelian malformation syndrome including oral clefts (Salahshourifar et al, ).…”

Syndrome de Van der Woude : un cas familial

“…La transmission se fait selon le mode autosomique dominant, avec une forte pénétrance (80 à 97 %) [3,4]. Le SVW est lié à une mutation des locus 1q32-q41 codant pour le gène IRF6 (Interferon Regulator Factor 6) [5][6][7], dont de multiples mutations ont été décrites [6,8]. Ce facteur est fortement impliqué dans le développement embryonnaire de la face [9].…”