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.