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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Association between homeobox-containing gene MSX1 and the occurrence of limb deficiency.

Animal studies have suggested an important role for the homeobox-containing gene MSX1 in limb, oralfacial, and cardiac malformations. In this study of 516 Caucasians with isolated birth defects registered in the Maryland Birth Defects Reporting and Information System (BDRIS), we report an association between a dinucleotide repeat polymorphism in MSX1 and isolated limb deficiency. Frequencies of rare alleles at the MSX1 locus are significantly higher among 34 infants with limb deficiency compared to 482 infants with other isolated birth defects (oral clefts, dislocation of hip, clubfoot, hypospadias, polydactyly, or syndactyly) (chi2 = 11.0, df = 3, P = 0.012). Infants carrying the rare alleles had a 4.81-fold higher risk of a limb deficiency when the mother reported smoking during pregnancy, compared to infants who are homozygous for the common allele and whose mother did not smoke. The significance of this apparent gene-environment interaction is attributed to infants with malformation of the lower limb. The statistical association and potential gene-environment interaction observed in this study (which was originally designed to investigate oral clefts) are compatible with results from animal studies involving the MSX1 gene, and suggests that further investigation into biological mechanisms is warranted.[1]


  1. Association between homeobox-containing gene MSX1 and the occurrence of limb deficiency. Hwang, S.J., Beaty, T.H., McIntosh, I., Hefferon, T., Panny, S.R. Am. J. Med. Genet. (1998) [Pubmed]
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