Evidence for a microdeletion in 1q32–41 involving the gene responsible for Van der Woude syndrome

Sander, Achim; Schmelzle, R.; Murray, Jon

doi:10.1093/hmg/3.4.575

Cited by 59 publications

(48 citation statements)

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“…The de novo deletion spanned the entire IRF6 gene. There are at least four other documented cases which involve deletion (19)(20)(21)(22). We are designing assays to map the size of the deletion and the exact breakpoints for this chromosomal region.…”

Section: Discussionmentioning

confidence: 99%

Identification of IRF6 gene variants in three families with Van der Woude syndrome

Tan¹,

Lim²,

Yap³

et al. 2008

Int J Mol Med

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Abstract.Van der Woude syndrome is the most common cause of syndromic orofacial clefting. It is characterised by the presence of lip pits, cleft lip and/or cleft palate. It is transmitted in an autosomal dominant manner, with high penetrance and variable expressivity. Several mutations in the interferon regulatory factor 6 (IRF6) gene have been found in VWS families, suggesting that this gene is the primary locus. We screened for mutations in this gene in three families in our population. There was a recurrent nonsense mutation within exon 9 of the gene for a Malay family consisting of five affected members with different presentations. We also found a co-segregating rare polymorphism which would result in a non-synonymous change 23 bases downstream of the nonsense mutation. This polymorphism was present in <1% of the Malay subjects screened, but was not found among the Chinese and Indians in our population. For another family, a 396C¡T mutation (R45W in the DNA-binding domain) was found in the proband, although the possibility of a genetic defect elsewhere could not be excluded because his mother and twin sister (both unaffected) also had this variant. In the third case with complete absence of family history, a de novo deletion spanning the whole IRF6 gene was detected in the child with VWS. This case of haploinsufficiency caused disruption of orofacial development but not other organ systems as the child has no other medical or developmental abnormalities despite the deletion of at least five other genes.

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Section: Discussionmentioning

confidence: 99%

Identification of IRF6 gene variants in three families with Van der Woude syndrome

Tan¹,

Lim²,

Yap³

et al. 2008

Int J Mol Med

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“…A 17,162-bp DNA fragment was deleted. The underlined nucleotides in the 5¢-boundary were identical to that in the 3¢-boundary families (Bocian and Walker 1987;Houdayer et al 2000;Sander et al 1994;Schutte et al 1999). Small deletions within or around the IRF6 gene, which were microscopically undetectable, also contributed to the disease, as demonstrated in this report.…”

Section: Discussionmentioning

confidence: 99%

“…Chromosomal microdeletion has also been reported to cause VWS in a subset of patients (Bocian and Walker 1987;Houdayer et al 2000;Sander et al 1994;Schutte et al 1999). An analysis of microsatellite markers has revealed a 350-kb critical region of VWS (Schutte et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Novel IRF6 mutations in Japanese patients with Van der Woude Syndrome: two missense mutations (R45Q and P396S) and a 17-kb deletion

et al. 2003

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Three Japanese families with Van der Woude syndrome (VWS) were screened for mutations in the interferon regulatory factor 6 gene (IRF6) by sequencing its entire coding region. Two novel missense mutations, R45Q in exon 3 and P396S in exon 9, were identified in families 1 and 2, respectively. In family 3, no causative base change was found by the sequencing analysis, but a deletion involving exons 4-9 was suggested by multiplex PCR analysis. To confirm the deletion and to determine its 5¢-and 3¢-boundaries, we amplified a DNA fragment containing a heterozygous polymorphic site in exon 2 by using a 5¢-upstream forward PCR primer and eight different reverse primers located 3¢-downstream of exon 2. The amplified product was subjected to nested PCR to generate a DNA fragment containing the polymorphic site. When a reverse primer located within the deletion was used for the first PCR amplification, only the nondeletion allele was detected after the second PCR. Repeated analyses with eight different reverse primers allowed us to map the boundaries of the deletion, and subsequently a heterozygous 17,162-bp deletion involving exons 4-9 was identified. Since IRF6 mutations in a significant portion of VWS patients remain undetected by conventional sequencing analysis, it may be important to search for a large deletion in those patients. Our simple methods to identify deletions and to determine the boundaries of a deletion would facilitate the identification of such patients.

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“…It was originally discovered studying a patient with typical features and a 1q32-41 deletion (Bocian & Walker, 1987). Sander et al (1994) found allele loss of a stable and highly polymorphic microsatellite (D1S205) of the 1q32-41 region in one family with Van der Woude syndrome. Schutte et al (1999) mapped a new deletion and showed that it extended 0n2-1 Mb beyond the proximal breakpoint of the deletion previously described.…”

mentioning

confidence: 99%

Linkage analysis of three candidate regions of chromosome 1 in nonsyndromic familial orofacial cleft

Martinelli

Scapoli

Pezzetti

et al. 2001

Annals of Human Genetics

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Linkage analysis and mouse model knockout studies indicate that loci\genes mapping in different chromosome 1 regions are good candidates for nonsyndromic orofacial cleft (OFC) malformation. On this basis, three different regions of the chromosome 1 have been analysed, by linkage analysis, in 38 families with nonsyndromic OFC. Positive scores were obtained by pairwise analysis and a nonparametric linkage approach for the 1p36 region, with markers close to the MTHFR locus. Additional results allowed us to exclude the presence of an OFC susceptibility gene in the 1q21 and 1q32-42n3 regions.

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Evidence for a microdeletion in 1q32–41 involving the gene responsible for Van der Woude syndrome

Cited by 59 publications

References 0 publications

Identification of IRF6 gene variants in three families with Van der Woude syndrome

Identification of IRF6 gene variants in three families with Van der Woude syndrome

Novel IRF6 mutations in Japanese patients with Van der Woude Syndrome: two missense mutations (R45Q and P396S) and a 17-kb deletion

Linkage analysis of three candidate regions of chromosome 1 in nonsyndromic familial orofacial cleft

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