Preimplantation genetic diagnosis for hereditary endocrine disease

To describe the process of preimplantation genetic diagnosis (PGD), which allows the selection of embryos without mutations for implantation, with specific application for mutations in GNAS.

We identified a GNAS mutation in a patient with a severe form of Albright hereditary osteodystrophy and pseudohypoparathyroidism type 1a with phocomelia and performed PGD on embryos derived by in vitro fertilization in order to deliver an unaffected infant.

After in vitro fertilization, embryos that were homozygous normal for GNAS were identified and implanted into the mother. Ultrasonography 34 days after embryo transfer showed a viable singleton intrauterine pregnancy. A normal-appearing male infant was born at 36.5 weeks of gestation. Newborn screening revealed normal results of thyroid function tests, and a buccal swab obtained when the child was 1 year old verified normal GNAS gene sequences.

PGD is an alternative that can be offered for many genetic diseases and represents a method to decrease and potentially eliminate the transmission of severe genetic diseases. Patients with multiple endocrine neoplasia (MEN) type 2 with known RET gene mutations as well as those with other heritable disorders are candidates for PGD. Successful PGD in patients with MEN has not yet been reported and has met with some early difficulties, but it is believed that this technique will eventually be successful for MEN and other hereditary endocrine disorders.