Refinement of the Van der Woude Gene Location and Construction of a 3.5-Mb YAC Contig and STS Map Spanning the Critical Region in 1q32–q41

doi:10.1006/geno.1996.0496

Genomics

Volume 36, Issue 3, 15 September 1996, Pages 507-514

https://doi.org/10.1006/geno.1996.0496 Get rights and content

Abstract

Van der Woude syndrome (VWS) is the most frequent form of syndromic clefting. Linkage analysis has localized the gene between D1S245 and D1S414, an interval of 4.1 cM with the following order of loci: centromere–D1S245/D1S471–D1S491–D1S205–D1S414–telomere. A microdeletion around D1S205 aided in narrowing the critical region to D1S491–D1S414 by heterozygosity testing. In this study, the location was refined by detection of a recombinant with D1S205 in a new family, indicating that VWS lies between D1S491 and D1S205, a 1.6-cM interval. A roughly 3.5-Mb YAC contig was built from D1S245 through D1S414, encompassing the interval D1S491–D1S205 in level 1 or level 2 paths. Clones were assembled by sequence tagged site (STS) content using the five polymorphic markers from above, four novel STSs identified from YAC ends, and a new STS derived from probe CRI-L461 (D1S70). D1S70 was assigned to the critical region. One single YAC, yCEPH785B2, contains both flanking STSs (D1S491, D1S205). STS content mapping suggests neither chimerism nor deletion of yCEPH785B2 but does suggest that the maximum size of the critical region is approximately 850 kb. All STSs were tested for their presence on a somatic cell hybrid containing the microdeleted chromosome 1 as the sole human chromosome 1 component. Both the proximal and distal ends of the microdeletion mapped to the 850-kb YAC, yCEPH785B2. Therefore, the microdeletion overlapped the critical region, confirming the genetic recombinant data.

References (0)

Cited by (41)

Orthodontic treatment in a patient with Van der Woude's syndrome
2006, American Journal of Orthodontics and Dentofacial Orthopedics
Van der Woude’s syndrome (VDW; #OMIM 119300) is an autosomal dominant disease characterized by cleft lip and/or palate and lower lip pit (fistula). The precise skeletal characteristics are unclear, and there have been no case reports of orthodontic treatment of patients with VDW. The Japanese girl whose treatment is reported here had VDW, including bilateral cleft lip and palate and bilateral symmetric lower lip pits. Orthodontic treatment started when she was just 3 years old, with a removable maxillary expansion appliance, followed by an edgewise multibracket appliance in both arches. Retention began at 11 years of age, and a secondary bone graft was performed for the alveolar cleft. She received prosthetic treatment and achieved a desirable occlusion at 18 years of age. Early intervention helped achieve a satisfactory treatment result for our patient. In contrast, her mother also had VDW, with a severe Class III skeletal pattern, but she had not been treated orthodontically; she had an anterior and lateral crossbite even after prosthetic treatment. The pretreatment characteristics of 4 other subjects with VDW are discussed; they show wide variations in the sizes of the maxilla and the mandible, suggesting that a common skeletal pattern is not generally seen in VDW.
A novel mutation of the IRF6 gene in an Italian family with Van der Woude syndrome
2004, Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Van der Woude syndrome (VWS) is the most common type of syndromic orofacial cleft, being characterised by variable association of lower lip pits, cleft lip and cleft palate. VWS is transmitted in an autosomal dominant manner, with high penetrance and variable expressivity, and a gene for this disease has been mapped in 1q32-q41. Very recently, mutations of the interferon regulatory factor 6 (IRF6) gene have been found in VWS patients, suggesting that this gene plays an important role in the orofacial development. We report a novel mutation of the IRF6 in an Italian family with six members affected by VWS with different expression. This mutation, the W217X, produces a stop codon within exon 6 of the IRF6 gene, with loss of the SMIR domain of the IRF6 protein.
Genetic models and approaches to study orofacial clefts
2022, Oral Diseases
Causes of phenotypic variability and disabilities after prenatal viral infections
2021, Tropical Medicine and Infectious Disease
Toward an orofacial gene regulatory network
2016, Developmental Dynamics
Sequencing of the interferon regulatory factor 6 (IRF6) gene and correlation to its phenotypes in familial non-syndromic cleft lip and palate in North Indian population
2014, European Journal of Plastic Surgery

View all citing articles on Scopus

^☆: Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession No.

^†: Deceased.

¹: To whom correspondence and reprint requests should be addressed at Department of Pediatrics, University of Iowa, Iowa City, IA 52242-1083, USA. Fax: (319) 335-6970. E-mail: [email protected].

View full text

Regular ArticleRefinement of the Van der Woude Gene Location and Construction of a 3.5-Mb YAC Contig and STS Map Spanning the Critical Region in 1q32–q41☆

Abstract

Regular Article
Refinement of the Van der Woude Gene Location and Construction of a 3.5-Mb YAC Contig and STS Map Spanning the Critical Region in 1q32–q41☆