Alternative titles; symbols
ORPHA: 141291, 199302, 199306; DO: 0080399;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 4p16.2 | Orofacial cleft 5 | 608874 | Autosomal dominant | 3 | MSX1 | 142983 |
A number sign (#) is used with this entry because of evidence that orofacial cleft-5 (OFC5) is caused by mutation in the MSX1 gene (142983) on chromosome 4p16.
For a phenotypic description and a discussion of genetic heterogeneity of nonsyndromic CL/P, see 119530.
With both case-control- and nuclear family-based approaches, Lidral et al. (1998) screened candidate genes for clefting in both the CL/P CPO of the nonsyndromic type. Significant linkage disequilibrium was found between CL/P and both MSX1 and TGFB3 (190230) 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 (126255), MSX1, and TGFB3 was performed in 69 CPO patients and in a subset of 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 their function.
Van den Boogaard et al. (2000) identified a stop codon in the MSX1 gene (142983.0002) in a 3-generation Dutch family with tooth agenesis and combinations of cleft palate only and cleft lip and cleft palate, providing further evidence for this gene in orofacial clefting. Scapoli et al. (2002) were unable to confirm the involvement of the MSX1 gene in nonsyndromic CL/P.
In 3 of 242 Filipinos with cleft lip/palate, Jezewski et al. (2003) identified a mutation in the MSX1 gene (142983.0004). One patient had unilateral cleft lip/palate; a second had bilateral cleft lip/palate; and the third had isolated cleft lip.
In 1 of 110 Uruguayan patients with cleft lip/palate, Jezewski et al. (2003) identified a mutation in the MSX1 gene (142983.0005). There was no family history of cleft lip/palate.
Suzuki et al. (2004) and Vieira et al. (2005) identified a missense mutation in the MSX1 gene (P147Q; 142983.0007) in Vietnamese and Filipino CL/P patients, respectively; however, Tongkobpetch et al. (2006) identified the variant in both Thai patients with nonsyndromic CL/P as well as normal Thai controls. Tongkobpetch et al. (2006) suggested that the P147Q variant is not pathogenic.
Jezewski, P. A., Vieira, A. R., Nishimura, C., Ludwig, B., Johnson, M., O'Brien, S. E., Daack-Hirsch, S., Schultz, R. E., Weber, A., Nepomucena, B., Romitti, P. A., Christensen, K., Orioli, I. M., Castilla, E. E., Machida, J., Natsume, N., Murray, J. C. Complete sequencing shows a role for MSX1 in non-syndromic cleft lip and palate. J. Med. Genet. 40: 399-407, 2003. [PubMed: 12807959] [Full Text: https://doi.org/10.1136/jmg.40.6.399]
Lidral, A. C., Romitti, P. A., Basart, A. M., Doetschman, T., Leysens, N. J., Daack-Hirsch, S., Semina, E. V., Johnson, L. R., Machida, J., Burds, A., Parnell, T. J., Rubenstein, J. L. R., Murray, J. C. Association of MSX1 and TGFB3 with nonsyndromic clefting in humans. Am. J. Hum. Genet. 63: 557-568, 1998. [PubMed: 9683588] [Full Text: https://doi.org/10.1086/301956]
Scapoli, L., Martinelli, M., Pezzetti, F., Carinci, F., Bodo, M., Tognon, M., Carinci, P. Linkage disequilibrium between GABRB3 gene and nonsyndromic familial cleft lip with or without cleft palate. Hum. Genet. 110: 15-20, 2002. [PubMed: 11810291] [Full Text: https://doi.org/10.1007/s00439-001-0639-5]
Suzuki, Y., Jezewski, P. A., Machida, J., Watanabe, Y., Shi, M., Cooper, M. E., Viet, L. T., Tin, N. T. D., Hai, H., Natsume, N., Shimozato, K., Marazita, M. L., Murray, J. C. In a Vietnamese population, MSX1 variants contribute to cleft lip and palate. Genet. Med. 6: 117-125, 2004. [PubMed: 15354328] [Full Text: https://doi.org/10.1097/01.gim.0000127275.52925.05]
Tongkobpetch, S., Siriwan, P., Shotelersuk, V. MSX1 mutations contribute to nonsyndromic cleft lip in a Thai population. J. Hum. Genet. 51: 671-676, 2006. [PubMed: 16868654] [Full Text: https://doi.org/10.1007/s10038-006-0006-4]
van den Boogaard, M.-J. H., Dorland, M., Beemer, F. A., Ploos van Amstel, H. K. MSX1 mutation is associated with orofacial clefting and tooth agenesis in humans. (Letter) Nature Genet. 24: 342-343, 2000. Note: Erratum: Nature Genet. 25: 125 only, 2000. [PubMed: 10742093] [Full Text: https://doi.org/10.1038/74155]
Vieira, A. R., Avila, J. R., Daack-Hirsch, S., Dragan, E., Felix, T. M., Rahimov, F., Harrington, J., Schultz, R. R., Watanabe, Y., Johnson, M., Fang, J., O'Brien, S. E., Orioli, I. M., Castilla, E. E., FitzPatrick, D. R., Jiang, R., Marazita, M. L., Murray, J. C. Medical sequencing of candidate genes for nonsyndromic cleft lip and palate. PLos Genet. 1: e64, 2005. Note: Electronic Article. [PubMed: 16327884] [Full Text: https://doi.org/10.1371/journal.pgen.0010064]