Pathological variant of OFD1 gene identified in a pedigree affected with oral-facial-digital syndrome type 1

Objective: To detect pathological variant in a Chinese pedigree affected with oral-facial-digital syndrome type 1 (OFD1).

Methods: Whole-exome sequencing was used to scan the whole exome of the proband. Potential variant of the OFD1 gene was also detected in all members of the pedigree and 100 healthy controls by Sanger sequencing. X chromosome inactivation analysis was performed. With the determination of the genotype, prenatal diagnosis was carried out by amniotic fluid sampling.

Results: A c.1189_1192delAATC (p. Q398Lfs*2) variant was identified in the OFD1 gene of the proband, other patients from this pedigree, as well as the fetus. The same variant was not found among healthy members from this pedigree and the 100 healthy controls. X chromosome inactivation analysis identifies the pregnant woman and her younger sister both had a non-random inactivation, other women patients had a random inactivation.

Conclusions: The c.1189_1192delAATC (p. Q398Lfs*2) variant of the OFD1 gene probably underlies the pathogenesis in this case. The new variant has enriched pathological spectrum of the OFD1 gene. The reason of intrafamilial clinical variability still need to be further confirmed.