Genetic Testing and Counseling for Pseudohypoparathyroidism Type Ib
Date Issued
2011
Date
2011
Author(s)
Chen, Yu-Wei
Abstract
Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders characterized by hypocalcemia, hyperphosphatemia, increased serum concentration of parathyroid hormone (PTH), and insensitivity to the biological activity of PTH.
The two main subtypes of pseudohypoparathyroidism (PHP), PHP Ia and PHP Ib, are caused by mutations in GNAS exons 1–13 and methylation defects in the imprinted GNAS cluster, respectively. PHP Ia patients show Albright hereditary osteodystrophy (AHO) and resistance toward multiple hormones (PTH/TSH/GHRH/gonadotropins), whereas PHP Ib patients classically display hormone resistance limited to PTH and TSH.
GNAS, the gene mainly encoding α subunit of the heterotrimeric stimulatory G protein, called Gsα. Gsα protein plays an important part of the endocrine signal transduction pathway.
Patients with PHP Ia present with a characteristic phenotype, collectively called AHO. The constellation of findings includes short stature, stocky habitus, obesity, developmental delay, round face, dental hypoplasia, brachymetacarpals, brachymetatarsals, and soft tissue calcification/ossification. Therefore, in addition to clinical diagnosis by laboratory biochemical tests, imaging and genetic diagnosis, patients can be diagnosis faster by the clinical characteristic observation.
Patients with PHP Ib lack features of AHO, have normal expression of Gsα protein in accessible tissues, and manifest hormonal resistance limited to PTH target tissues. PTH resistance may be limited to the kidney, with PTH responsiveness preserved in the bone, as evidenced by the hyperparathyroid skeletal lesions observed in these patients. It is difficult to diagnosis by clinical characteristic observation. Therefore, the hope that through the establishment of genetic testing methods to provide future clinical molecular diagnostic techniques and genetic counseling services platform. Furthermore, we hope that the future of prenatal diagnosis on the patient can bring more help.
Subjects
Pseudohypoparathyroidism type Ib
GNAS locus
Gsα protein
Hypocalcemia
Hyperphosphatemia
Elevated serum PTH
AHO (Albright hereditary osteodystrophy)
SDGs
Type
thesis
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