title: [Mutation analysis for two hypophosphatasia families with targeted next-generation sequencing].
abstract: Objective:To detect the mutations in alkaline phosphatase (ALPL) gene of two Chinese families with perinatal hypophosphatasia (HPP), in order to explore the mechanism of this condition.Methods:Next-generation sequencing (NGS) of osteology system panel was carried out for exome sequencing in the mothers of 2 HPP fetuses, who visited Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University. Further polymerase chain reaction (PCR) and Sanger sequencing validation was performed in the parents, affected fetuses and 200 unrelated healthy individuals to verify the mutation sites.Results:The mother and father of No.1 family carried ALPL gene c. 333delC (p.Gly112AlafsX10) and c. 568_570delAAC (p.190delAsn) base deletions, respectively. The affected fetus carried compound heterozygotes of the two mutations. Two mutations in ALPL gene known to be associated with hypophosphatasia were found in No.2 family, c. 1250A>G (p.Asn417Ser) in the mother and c. 1166C>A (p.Thr389Asn) in the father, while the fetus was a compound heterozygote carrying both of the two mutations. Both families met the pattern of autosomal recessive inheritance. ALPL gene c. 333delC (p.Gly112AlafsX10) was a novel mutation, and it was not found in the 200 unrelated healthy individuals.Conclusions:The mutations in ALPL gene may be the cause of HPP in the 2 families. NGS technology combined with Sanger sequencing could be an efficient and accurate diagnostic method.
authors.affiliation: *Prenatal Diagnosis Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Bai
authors.forename: N
authors.initials: N
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: X D
authors.initials: XD
authors.lastname: Kong
mesh_terms: D000469:Alkaline Phosphatase; D044466:Asian People; D004252:DNA Mutational Analysis; D005260:Female; D005333:Fetus; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007014:Hypophosphatasia; D009154:Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis; D017384:Sequence Deletion
chemical_list: D000469:Alkaline Phosphatase