ABSTRACT
Neural tube defects (NTD) are a common birth defect, with both genetic and environmental contributions to their etiology. In mouse, null mutations in Noggin result in fully-penetrant NTDs. We investigated Noggin for mutations that may predispose to human NTDs in 202 NTD cases. One variant allele was identified in a male patient with myelomeningocele. The patient's father and a sibling also carried the variant allele, but neither was affected with an open NTD. DNA sequencing confirmed a C1064A missense mutation predicted to result in the conversion of residue 84 from proline to histidine. The variant found in the NTD patient is a newly identified variant, the role of which is uncertain.
Subject(s)
Bone Morphogenetic Proteins/genetics , Genetic Predisposition to Disease , Mutation , Neural Tube Defects/genetics , Carrier Proteins , Chromatography, High Pressure Liquid , Female , Humans , Male , Meningomyelocele/geneticsABSTRACT
We investigated the T locus as a candidate gene in a series of patients and families with lumbosacral myelomeningocele. Single-strand conformation polymorphism (SSCP) analysis was used to identify sequence variation in all 8 exons and in intron 7 of this locus. We found evidence of substantial polymorphism within this locus, as previously reported [Papapetrou et al., 1999, J Med Genet 36:208-213], and moderately significant evidence of linkage disequilibrium with the CacI polymorphism of exon 8. However, when the locus was considered as a whole, with all single nucleotide polymorphisms (SNPs) integrated into a haplotype, there was no evidence for linkage disequilibrium. In addition, we did not identify any new sequence variants. Thus, we conclude that the T locus is not a major locus for human NTDs in this sample.
