Maternal Imprinting in Pseudohypoparathyroidism - A Very Rare GNAS Gene Mutation Follows the Pattern

Excerpt

To the Editor: An 11-y-old boy presented with carpopedal spasms for one day with elicitable Trousseau’s and Chvostek’s signs. Examination revealed round face and brachydactyly suggestive of Albright’s hereditary osteodystrophy (AHO). Investigations showed hypocalcemia (5.4 mg/dL), hyperphosphatemia (11.2 mg/dL), elevated alkaline phosphatase (424 U/L) and parathormone (444.7 pg/mL) with normal 25-hydroxy vitamin D, serum magnesium and short metatarsals on X-ray. He was born small for gestational age (SGA) at term (2.25 kg). Levothyroxine was initiated for hypothyroidism in infancy. Computed Tomography of the Brain showed basal ganglia calcifications. Exome sequencing revealed a pathogenic heterozygous 4 base pair deletion in exon 7 of the GNAS gene that resulted in a frameshift mutation (chr20:g.58909194_58909197delICTGA) leading to premature truncation of the protein (p.Asp832MetfsTer14), confirming the clinical diagnosis of pseudohypoparathyroidism (PHP). He was treated for hypocalcemia and hyperphosphatemia with calcium, calcitriol and sevelamer carbonate respectively. His asymptomatic mother had phenotypic AHO features similar to the child with normal serum investigations. She was diagnosed with pseudopseudohypoparathyroidism (PPHP) and confirmed to carry the GNAS variant reported in her son. …