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Confirmation of linkage of Van der Woude syndrome to chromosome 1q32: evidence of association with STR alleles suggests possible unique origin of the disease mutation.
J Craniofac Genet Dev Biol. 1999 Jul-Sep; 19(3):128-34.JC

Abstract

Van der Woude syndrome (VWS) is an autosomal dominant craniofacial disorder with high penetrance and variable expression. Its clinical features are variably expressed, but include cleft lip and/or cleft palate, lip pits and hypodontia. All VWS families studied to date map the disease gene to a < 2 cM region of chromosome 1q32, with no evidence of locus heterogeneity. The aim of this study is to refine the localization of the VWS gene and to further assess possible heterogeneity. We analyzed four multiplex VWS families. All available members were clinically assessed and genotyped for 19 short tandem repeat markers on chromosome 1 in the VWS candidate gene region. We performed two-point and multipoint limit of detection (LOD) score analyses using a high penetrance autosomal dominant model. All families showed positive LOD scores without any recombination in the candidate region. The largest two-point LOD score was 5.87. Our assay method for short tandem repeat (STR) markers provided highly accurate size estimation of marker allele fragment sizes, and therefore enabled us to determine the specific alleles segregating with the VWS gene in each of our four families. We observed a striking pattern of STR allele sharing at several closely linked loci among our four Caucasian VWS families recruited at three different locations in the US. These results suggest the possibility of a unique origin for a mutation responsible for many or most cases of VWS.

Authors+Show Affiliations

Department of Pediatrics and Pathology, University of Nebraska Medical Center, Omaha, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10589394

Citation

Beiraghi, S, et al. "Confirmation of Linkage of Van Der Woude Syndrome to Chromosome 1q32: Evidence of Association With STR Alleles Suggests Possible Unique Origin of the Disease Mutation." Journal of Craniofacial Genetics and Developmental Biology, vol. 19, no. 3, 1999, pp. 128-34.
Beiraghi S, Miller-Chisholm A, Kimberling WJ, et al. Confirmation of linkage of Van der Woude syndrome to chromosome 1q32: evidence of association with STR alleles suggests possible unique origin of the disease mutation. J Craniofac Genet Dev Biol. 1999;19(3):128-34.
Beiraghi, S., Miller-Chisholm, A., Kimberling, W. J., Sun, C. E., Wang, Y. F., Russell, L. J., Khoshnevisan, M., Storm, A. L., Long, R. E., Witt, P. D., Mazaheri, M., & Diehl, S. R. (1999). Confirmation of linkage of Van der Woude syndrome to chromosome 1q32: evidence of association with STR alleles suggests possible unique origin of the disease mutation. Journal of Craniofacial Genetics and Developmental Biology, 19(3), 128-34.
Beiraghi S, et al. Confirmation of Linkage of Van Der Woude Syndrome to Chromosome 1q32: Evidence of Association With STR Alleles Suggests Possible Unique Origin of the Disease Mutation. J Craniofac Genet Dev Biol. 1999 Jul-Sep;19(3):128-34. PubMed PMID: 10589394.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Confirmation of linkage of Van der Woude syndrome to chromosome 1q32: evidence of association with STR alleles suggests possible unique origin of the disease mutation. AU - Beiraghi,S, AU - Miller-Chisholm,A, AU - Kimberling,W J, AU - Sun,C E, AU - Wang,Y F, AU - Russell,L J, AU - Khoshnevisan,M, AU - Storm,A L, AU - Long,R E,Jr AU - Witt,P D, AU - Mazaheri,M, AU - Diehl,S R, PY - 1999/12/10/pubmed PY - 2001/3/28/medline PY - 1999/12/10/entrez SP - 128 EP - 34 JF - Journal of craniofacial genetics and developmental biology JO - J Craniofac Genet Dev Biol VL - 19 IS - 3 N2 - Van der Woude syndrome (VWS) is an autosomal dominant craniofacial disorder with high penetrance and variable expression. Its clinical features are variably expressed, but include cleft lip and/or cleft palate, lip pits and hypodontia. All VWS families studied to date map the disease gene to a < 2 cM region of chromosome 1q32, with no evidence of locus heterogeneity. The aim of this study is to refine the localization of the VWS gene and to further assess possible heterogeneity. We analyzed four multiplex VWS families. All available members were clinically assessed and genotyped for 19 short tandem repeat markers on chromosome 1 in the VWS candidate gene region. We performed two-point and multipoint limit of detection (LOD) score analyses using a high penetrance autosomal dominant model. All families showed positive LOD scores without any recombination in the candidate region. The largest two-point LOD score was 5.87. Our assay method for short tandem repeat (STR) markers provided highly accurate size estimation of marker allele fragment sizes, and therefore enabled us to determine the specific alleles segregating with the VWS gene in each of our four families. We observed a striking pattern of STR allele sharing at several closely linked loci among our four Caucasian VWS families recruited at three different locations in the US. These results suggest the possibility of a unique origin for a mutation responsible for many or most cases of VWS. SN - 0270-4145 UR - https://www.unboundmedicine.com/medline/citation/10589394/Confirmation_of_linkage_of_Van_der_Woude_syndrome_to_chromosome_1q32:_evidence_of_association_with_STR_alleles_suggests_possible_unique_origin_of_the_disease_mutation_ L2 - http://www.diseaseinfosearch.org/result/7346 DB - PRIME DP - Unbound Medicine ER -