Synpolydactyly in a Chinese kindred: mutation detection, prenatal ultrasonographic and molecular diagnosis

Abstract

To identify potential mutation responsible for synpolydactyly (SPD) in a large Chinese kindred and to offer genetic counseling and prenatal diagnosis for the members of the family. All family members were examined clinically, and blood samples were obtained for linkage analysis and mutation screening. Ultrasound examinations were conducted at 16-21 weeks. Amniotic fluid sample was obtained by ultrasound-guided amniocentesis at 18 weeks of gestation. A large kindred affected with SPD was identified and characterized. With two short tandem repeat (STR) markers (D2S1238 and D2S1245) flanking the HOXD13 gene, the disease was mapped to 2q31. A heterozygous 27 bp expansion within the imperfect GCN triplet-repeat of exon 1, c. 184_210dup, was identified. The mutation resulted in a gain of 9 alanine residues between the 14th and 15th alanine of the normal 15-amino-acid-long polyalanine tract. On ultrasound examination, all fingers and toes of the fetus appeared to be normal. Linkage analysis and mutation detection confirmed that the fetus did not inherit the mutant allele from his affected mother. HOXD13 gene mutation was responsible for the SPD phenotype in this family. Accurate prenatal diagnosis of SPD was achieved with combined ultrasound and molecular analysis.