Preimplantation Genetic Diagnosis for Severe Albright Hereditary Osteodystrophy

Context: Preimplantation genetic diagnosis (PGD) enables the selection of embryos without mutations for implantation and has not been described to our knowledge for mutations in GNAS. Phocomelia in a patient with Albright hereditary osteodystrophy (AHO) has also not been previously described. Objective: The aim of this study was to identify a GNAS mutation in a patient with a severe form of AHO and pseudohypoparathyroidism type 1a with phocomelia and to perform PGD on embryos derived by in vitro fertilization to deliver an unaffected infant. Design: A proband and his family are described clinically, the GNAS gene was sequenced to identify a novel mutation in the proband, and PGD was performed on embryos. Setting: The setting was in a tertiary-care hospital. Patients: The patients were from a single family in which the proband has a severe form of AHO. Interventions: Interventions were PGD and in vitro fertilization. Main Outcome Measures: The main outcome measures were the clinical phenotypes and GNAS gene sequences of the proband, embryos, and family members. Results: After PGD, three genotypically normal embryos were transferred back to the mother. Pregnancy ensued, and a healthy male infant was delivered at 36.5 wk gestation. The GNAS genes in the baby were confirmed as wild-type, and the infant is free of any signs of AHO. Conclusions: We describe herein a proband with AHO and severe skeletal deformities (including phocomelia) related to a novel GNAS mutation and the delivery of a male infant with homozygous normal GNAS genotype after PGD.