GNAS GENE ANALYSIS:

Albright hereditary osteodystrophy (AHO), Pseudohypoparathyroidism, type 1A (PHP1a), and Progressive Osseous Hyperplasia (POH) are metabolic disorders resulting from the reduced sensitivity of target tissues to parathyroid hormone and other hormones.  As a result, multiple organ systems may be affected. AHO and PHP1a result in various combinations of short stature, obesity, mental retardation, round face, brachydactyly and bone calcification. Other symptoms may include ectopic ossification, cataracts and dental hypoplasia. POH is characterized by extensive dermal ossification during childhood. McCune Albright syndrome, which may also be caused by mutations in the GNAS gene is discussed separately. 

These conditions have been found to be a result of mutations in the gene encoding the alpha subunit of the adenylate cyclase stimulatory G protein (GNAS) located at 20q13.2. Estimates of the proportion of PHP1a caused by GNAS mutations range form 60 to 90%. Causative mutations have been found throughout the 13-exon gene; however, about 35-50% of the mutations by incidence are a 4bp deletion in exon 7. Although the inheritance appears to be autosomal dominant, the issue is complicated by a potential complex form of tissue- and development-influenced imprinting in which PHP1a is almost always inherited from a maternal carrier; but cases of paternal inheritance have also been described. In contrast, POH is almost always paternally inherited.

• Obesity associated with brachydactyly.

• Ectopic ossification - especially in the skin.

• Family history of any of these conditions.

• Parathyroid hormone unresponsiveness.

• Patients with multiple endocrine defects.

• PCR amplification and DNA sequencing of exons 2-13 of the GNAS1 gene.

• Blood EDTA (purple top) tubes:  

            Newborn: minimum 1-2 mL          

            Child/Adult: prefer 2 tubes of 3-5 mL

• Prenatal testing: Please contact the laboratory for instructions.

TURNAROUND TIME:      3-4 weeks

CPT CODES: