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

被引：0

作者：

Sano, Shinichiro ^{[1
,2
,6
]}

Iwamoto, Shotaro ^{[3
]}

Matsushita, Rie ^{[4
]}

Masunaga, Yohei ^{[1
]}

Fujisawa, Yasuko ^{[2
]}

Ogata, Tsutomu ^{[2
,5
]}

机构：

[1] Shizuoka Childrens Hosp, Dept Pediat Endocrinol & Metab, Shizuoka, Japan

[2] Hamamatsu Univ, Sch Med, Dept Pediat, Hamamatsu, Japan

[3] Mie Univ, Total Care Ctr AYA Canc & Children, Tsu, Mie, Japan

[4] Kyoto Univ, Grad Sch Med & Publ Hlth, Dept Pharmacoepidemiol, Kyoto, Japan

[5] Hamamatsu Med Ctr, Dept Pediat, Hamamatsu, Japan

[6] Shizuoka Childrens Hosp, Dept Pediat Endocrinol & Metab, 860 Urushiyama,Aoi Ku, Shizuoka 4208660, Japan

来源：

CLINICAL PEDIATRIC ENDOCRINOLOGY | 2024年 / 33卷 / 02期

基金：

日本学术振兴会;

关键词：

pseudohypoparathyroidism; GNAS-Gs alpha; splice donor site mutation; nonsense-mediated mRNA decay; MUTATIONS; GENOTYPE; GENE;

D O I：

10.1297/cpe.33.2023-0065

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We encountered a Chinese girl with pseudohypoparathyroidism type 1A (PHP1A) and her mother with pseudopseudohypoparathyroidism (PPHP). Sequencing analysis of GNAS-Gs alpha 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.

引用

页码：66 / 70

页数：5

共 36 条

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