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A novel GNAS-Gsa splice donor site variant in a girl with pseudohypoparathyroidism type 1A and her mother with pseudopseudohypoparathyroidism.

Authors :
Shinichiro Sano
Shotaro Iwamoto
Rie Matsushita
Yohei Masunaga
Yasuko Fujisawa
Tsutomu Ogata
Source :
Clinical Pediatric Endocrinology. Apr2024, Vol. 33 Issue 2, p66-70. 5p.
Publication Year :
2024

Abstract

We encountered a Chinese girl with pseudohypoparathyroidism type 1A (PHP1A) and her mother with pseudopseudohypoparathyroidism (PPHP). Sequencing analysis of GNAS-Gsa revealed a heterozygous c.212+2T>C variant (NM_000516.4) affecting the canonical splice donor site of intron 2 in the girl and her mother. RT-PCR performed on mRNA samples obtained from cycloheximide-treated and cycloheximide-untreated lymphoblastoid cell lines of this girl revealed the utilization of an alternative splice donor site at 33-34 bp from the boundary between exon 2 and intron 2 and the production of an aberrant mRNA with a retention of a 32 bp intronic sequence between exon 2 and exon 3 (p.(Gly72Lysfs*39)), which satisfied the condition for the occurrence of nonsense-mediated mRNA decay, as predicted by SpliceAI. This study revealed the molecular consequences of disruption of the canonical splice donor site and confirmed the clinical utility of SpliceAI. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09185739
Volume :
33
Issue :
2
Database :
Academic Search Index
Journal :
Clinical Pediatric Endocrinology
Publication Type :
Academic Journal
Accession number :
178578667
Full Text :
https://doi.org/10.1297/cpe.2023-0065