Prenatal diagnosis of ALPL gene mutations in recurrent fetal skeletal dysplasia

Objective: One multiparity women had recurrent pregnancies of skeletal dysplasia. The karyotype and array-comparative genomic hybridization were unremarkable. Thus, trio whole exome sequencings were suggested. Case report: The ALPL gene mutations were identified. Maternal heterozygous deletion on Chr1: 21880592 (GRCh37) TA->T, paternal heterozygous insertion on Chr1 21894597, 21894598 (GRCh37) G->GC, T->TAA, and the compound heterozygous mutation were noted on her third pregnancy. The prenatal ultrasound findings and ALPL variants were compatible with the diagnosis of hypophosphatasia. Sanger sequencings were performed and found their normal phenotype daughter carried the same heterozygous mutation with her mother. The mother was then incidentally found her fourth pregnancy; unfortunately, the fetus was prenatally diagnosed of hypophosphatasia with the compound heterozygous mutations. Conclusion: The whole exome sequencing could assist to find the disease-causing variants, which may not be identified through routine prenatal diagnosis. With the precise diagnosis, we could provide the counseling for prenatal or pre-implantation diagnosis.