[Analysis of COL1A1 gene variants in five Chinese pedigrees affected with osteogenesis imperfecta]

To detect potential variants of COL1A1 gene in five Chinese pedigrees affected with osteogenesis imperfecta (OI) and provide prenatal diagnosis for a fetus at 11th gestational week.

The coding regions and exon/intron boundaries of 225 genes associated with bone diseases were subjected to targeted capture and next generation sequencing (NGS). Suspected mutations were verified with Sanger sequencing in the probands, unaffected relatives and 100 unrelated healthy controls. Prenatal diagnosis for a high-risk fetus was carried out by Sanger sequencing.

The probands of the pedigrees 1-5 have respectively carried c.3226G>A (p.Gly1076Ser), c.579delT (p.Gly194Valfs*71), c.2911-2912insAG (p.Gly971Glufs*138), c.3037G>A (p.Gly1013Arg) and c.642+5G>A variants of the COL1A1 gene. For pedigree 1, the same variant was not found in the fetus. c.3037G>A (p.Gly1013Arg) and c.2911-2912insAG (p.Gly971Glufs*138) were not reported previously.

Mutations of the COL1A1 gene probably underlie the OI in the five pedigrees. Combined NGS and Sanger sequencing can provide an effective and accurate method for the genetic and prenatal diagnosis of OI.