1. Genotype-Phenotype Correlation of GNAS Gene: Review and Disease Management of a Hotspot Mutation.
- Author
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Cipriano L, Ferrigno R, Andolfo I, Russo R, Cioffi D, Savanelli MC, Pellino V, Klain A, Iolascon A, and Piscopo C
- Subjects
- Child, Female, Humans, Male, Mutation, Phenotype, Pseudohypoparathyroidism diagnosis, Pseudohypoparathyroidism genetics, Pseudohypoparathyroidism therapy, Sequence Deletion, Brachydactyly diagnosis, Brachydactyly genetics, Brachydactyly therapy, Intellectual Disability diagnosis, Intellectual Disability genetics, Intellectual Disability therapy, Ossification, Heterotopic diagnosis, Ossification, Heterotopic genetics, Ossification, Heterotopic therapy, Chromogranins genetics, Genetic Association Studies, GTP-Binding Protein alpha Subunits, Gs genetics
- Abstract
Defects of the GNAS gene have been mainly associated with pseudohypoparathyroidism Ia. To date, pathogenic missense, frameshift, non-sense and splicing variants have been described in all the 13 exons of the GNAS gene. Of them, a specific mutation, namely the 4 bp deletion c.565_568delGACT, is currently considered a mutation hotspot. Recent articles performed genotype-phenotype correlations in patients with GNAS -related pseudohypoparathyroidism Ia (PHP1a) but a specific focus on this hotspot is still lacking. We reported two cases, from our department, of PHP1a associated with c.565_568delGACT deletion and performed a literature review of all the previously reported cases of the 4 bp deletion hotspot. We found a higher prevalence of brachydactyly, round face, intellectual disability and subcutaneous/heterotopic ossifications in patients with the c.565_568delGACT as compared to the other variants in the GNAS gene. The present study highlights the different prevalence of some clinical features in patients with the c.565_568delGACT variant in the GNAS gene, suggesting the possibility of a personalized diagnostic follow-up and surveillance for these patients.
- Published
- 2024
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