Infantile hypophosphatasia: Successful prenatal assessment by testing for tissue‐non‐specific alkaline phosphatase isoenzyme gene mutations

Paula S. Henthorn, Michael P. Whyte

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

We successfully assessed a fetus at risk for lethal infantile hypophosphatasia using amniocyte DNA and allele‐specific oligonucleotide (ASO) probes for two missense mutations in the tissue‐non‐specific alkaline phosphatase isoenzyme (TNSALP) gene. The nucleotide changes had been discovered in a sister who died at 8 months of age from this inborn error of metabolism. The mother was known to carry the 747 (cDNA) G→A transition, whereas her husband and 5‐year‐old daughter, who were also healthy, carried the 1309 A→T transversion. Amniocytes, obtained at 16 weeks' gestation, provided genomic DNA for polymerase chain reaction (PCR) amplification of the appropriate TNSALP gene exons. ASO hybridization revealed absence of the 747A mutation and presence of the 1309T base change in the fetus, indicating a carrier for hypophosphatasia. At 8 months of age, the offspring was in excellent health and without any radiological evidence of skeletal disease. His serum ALP activity and plasma pyridoxal 5′‐phosphate level were decreased and increased, respectively, at levels consistent with the prenatal assessment. The ASO studies were confirmed postnatally using peripheral blood leukocyte DNA. This is the first application of direct mutational analysis to assess a fetus at risk for hypophosphatasia.

Original languageEnglish
Pages (from-to)1001-1006
Number of pages6
JournalPrenatal Diagnosis
Volume15
Issue number11
DOIs
StatePublished - Nov 1995

Keywords

  • bone disease
  • rickets
  • vitamin B

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