Mutation screening in candidate genes in four Chinese brachydactyly families.
Autosomal dominant brachydactyly (BD) is a skeletal disorder with several subtypes, including brachydactyly type A1 (BDA1) and brachydactyly type B1 (BDB1). Mutations in Indian hedgehog (IHH) are usually associated with BDA1, whereas heterozygous mutations in receptor tyrosine kinase-like orphan receptor 2 (ROR2) are mainly responsible for BDB1. On the basis of the clinical phenotype identification, we screened IHH and ROR2 by the candidate gene approach using PCR direct sequencing. We found three known mutations of IHH (c.283_285delGAG, p.E95del; c.298 G>A, p.D100N; c.300C>G, p.D100E) in three Chinese families with BDA1, and a novel heterozygous nonsense mutation of ROR2 (c.2273C>A, p.S758X) in a BDB1 family. It was noted that c.300C>G mutation was a new nucleotide substitution compared to the reported c.300C>A, which led to the same amino acid change (p.D100E). The novel nonsense mutation p.S758X was verified by absence in the unaffected family members and the 100 randomly-selected controls. In this paper, we report three recurrent mutations with a new nucleotide substitution of IHH in three Chinese families with BDA1 and a novel nonsense mutation in BDB1 pedigree. We therefore recommend the approach of candidate gene screening as the first choice for genetic testing for BD.
['Dong|Sufang|S|', 'Wang|Yinghui|Y|', 'Tao|Shengxiang|S|', 'Zheng|Fang|F|']
D000328:Adult D044466:Asians D001483:Base Sequence D059327:Brachydactyly D004252:DNA Mutational Analysis D005190:Family D005260:Female D005528:Foot D056726:Genetic Association Studies D020022:Genetic Predisposition to Disease D006225:Hand D006801:Humans D008297:Male D008969:Molecular Sequence Data D010375:Pedigree D010641:Phenotype D018807:Polymorphism, Single-Stranded Conformational D011859:Radiography
BDA1 BDB1 IHH ROR2