Whole-genome sequencing revealed a novel long-range deletion mutation spanning GNAS in familial pseudohypoparathyroidism.

Abstract

BACKGROUND:

Pseudohypoparathyroidism (PHP) is a series of diseases related to pathological changes and neurocognitive and endocrine abnormalities, mainly due to the GNAS mutation on chromosome 20q13.2, which weakens receptor-mediated hormone signal transduction. Considering its complex genetic and epigenetic characteristics, GNAS may produce complex clinical phenotypes in families or sporadic cases. This study presented a case of familial PHP caused by a deletion mutation in the 20q13.2 region.

METHODS AND RESULTS:

The proband and her second daughter had PHP, and the proband's mother had pseudo-PHP. Whole-genome sequencing revealed that the proband had an 849.81 kb deletion spanning GNAS near the maternal 20q13.2 chromosome. Multiplex ligation-dependent probe amplification methylation analysis indicated that the proband as well as her mother and second daughter had seemingly abnormal GNAS methylation. This is different from the phenotype (feeding difficulty, slow growth, and special facial features) of previously reported cases with the deletion of fragments near the 20q13.2 chromosome.

CONCLUSIONS:

This report demonstrated the variability of 20q13.2 deletion phenotypes and the clinical importance of using multiple molecular genetic detection methods.

• Authors: Yangfan Fei, Lv Liu, Lixia Wu, Ou Wang, Xiaoping Xing, Aiping Li, Lingyi Huang
• Journal: Molecular genetics & genomic medicine (Mol Genet Genomic Med) Vol. 11 Issue 5 Pg. e2144 (05 2023) ISSN: 2324-9269 [Electronic] United States
• PMID: 36669868 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.

Chemical References

• GTP-Binding Protein alpha Subunits, Gs
• Chromogranins
• GNAS protein, human

Topics

• Female
• Humans
• GTP-Binding Protein alpha Subunits, Gs (genetics)
• DNA Methylation
• Chromogranins (genetics)
• Pseudohypoparathyroidism (genetics, diagnosis)
• Sequence Deletion