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Association of MSX1 and TGFB3 with nonsyndromic clefting in humans. Am J Hum Genet 1998 Aug;63(2):557-68

Date

07/31/1998

Pubmed ID

9683588

Pubmed Central ID

PMC1377298

DOI

10.1086/301956

Scopus ID

2-s2.0-0032231873 (requires institutional sign-in at Scopus site)   264 Citations

Abstract

Nonsyndromic cleft lip with or without cleft palate (CL/P) and nonsyndromic cleft palate only (CPO) are common congenital anomalies with significant medical, psychological, social, and economic ramifications. Both CL/P and CPO are examples of complex genetic traits. There exists sufficient evidence to hypothesize that disease loci for CL/P and CPO can be identified by a candidate-gene linkage-disequilibrium (LD) strategy. Candidate genes for clefting, including TGFA, BCL3, DLX2, MSX1, and TGFB3, were screened for LD with either CL/P or CPO in a predominantly Caucasian population, with both case-control- and nuclear-family-based approaches. Previously reported LD for TGFA with both CL/P and CPO could not be confirmed, except in CL/P patients with a positive family history. Also, in contrast to previous studies, no LD was found between BCL3 and either CL/P or CPO. Significant LD was found between CL/P and both MSX1 and TGFB3 and between CPO and MSX1, suggesting that these genes are involved in the pathogenesis of clefting. In addition, a mutation search in the genes DLX2, MSX1, and TGFB3 was performed in 69 CPO patients and in a subset of the CL/P patients. No common mutations were found in the coding regions of these genes; however, several rare variants of MSX1 and TGFB3 were found that may alter the latters' normal function. These results form the basis for future research, including (a) mutation searches in the MSX1 and TGFB3 genes in Caucasian CL/P patients and (b) extension of the search for MSX1 mutations in CPO patients to the noncoding regions.

Author List

Lidral AC, Romitti PA, Basart AM, Doetschman T, Leysens NJ, Daack-Hirsch S, Semina EV, Johnson LR, Machida J, Burds A, Parnell TJ, Rubenstein JL, Murray JC

Author

Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Substitution
Case-Control Studies
Cleft Lip
Cleft Palate
Exons
Genetic Markers
Genetic Variation
Homeodomain Proteins
Humans
Introns
Iowa
Linkage Disequilibrium
MSX1 Transcription Factor
Mutation
Nuclear Family
Open Reading Frames
Point Mutation
Transcription Factors
Transforming Growth Factor beta