1. Five patients with disorders of calcium metabolism presented with GCM2 gene variants
- Author
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Olaia Velasco, Alicia R. Martin, Carmen Lourdes Rey Cordo, Leire Madariaga, Luis Castaño, Inés Urrutia, Ignacio Goicolea, Yolanda Garcia-Fernández, Pedro Gonzalez, Idoia Martínez de LaPiscina, Sonia Gaztambide, Anibal Aguayo, Alejandro García-Castaño, Sara Gómez-Conde, Rosa de Diego Martínez, Ana Belén De la Hoz, Laura Saso, Gustavo Pérez de Nanclares, and María López-Iglesias
- Subjects
Male ,0301 basic medicine ,DNA Mutational Analysis ,parathyroid cells ,hypocalcemia ,Cohort Studies ,Endocrinology ,0302 clinical medicine ,Genetics ,Multidisciplinary ,calcium homeostasis ,High-Throughput Nucleotide Sequencing ,Nuclear Proteins ,hypoparathyroidism ,Parathyroid chief cell ,Middle Aged ,Hyperparathyroidism, Primary ,Parathyroid Hormone ,Medicine ,Female ,GCM2 gene in the heterozygous state ,Adult ,Heterozygote ,Adolescent ,Science ,chemistry.chemical_element ,030209 endocrinology & metabolism ,Disorders of calcium metabolism ,Calcium ,Biology ,Article ,Phosphorus metabolism ,Parathyroid Glands ,03 medical and health sciences ,disorders of phosphorus metabolism ,medicine ,Humans ,GCM2 ,Calcium Signaling ,Gene ,Germ-Line Mutation ,Aged ,Calcium metabolism ,Infant ,disorder of calcium metabolism ,medicine.disease ,030104 developmental biology ,Hypoparathyroidism ,chemistry ,Primary hyperparathyroidism ,Transcription Factors - Abstract
The GCM2 gene encodes a transcription factor predominantly expressed in parathyroid cells that is known to be critical for development, proliferation and maintenance of the parathyroid cells. A cohort of 127 Spanish patients with a disorder of calcium metabolism were screened for mutations by Next-Generation Sequencing (NGS). A targeted panel for disorders of calcium and phosphorus metabolism was designed to include 65 genes associated with these disorders. We observed two variants of uncertain significance (p.(Ser487Phe) and p.Asn315Asp), one likely pathogenic (p.Val382Met) and one benign variant (p.Ala393_Gln395dup) in the GCM2 gene in the heterozygous state in five families (two index cases had hypocalcemia and hypoparathyroidism, respectively, and three index cases had primary hyperparathyroidism). Our study shows the utility of NGS in unravelling the genetic origin of some disorders of the calcium and phosphorus metabolism, and confirms the GCM2 gene as an important element for the maintenance of calcium homeostasis. Importantly, a novel variant in the GCM2 gene (p.(Ser487Phe)) has been found in a patient with hypocalcemia. This study was supported by three grants from the Department of Health (2017111014, 2018111097 and 2019111052) and one grant from the Department of Education (IT1281-19) of the Basque Government. This work is generated within the Endocrine European Reference Network (Project ID number of Endo-ERN: 739527). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
- Published
- 2021
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