Exome sequencing identifies a novel frameshift variant causing hypomagnesemia with secondary hypocalcemia

CEN Case Reports
M Kamran AzimGhulam Mujtaba

Abstract

Hypomagnesemia with secondary hypocalcemia is a rare autosomal-recessive disorder characterized by intense hypomagnesemia associated with hypocalcemia (HSH). Mutations in the TRPM6 gene, encoding the epithelial Mg2+ channel TRPM6, have been proven to be the molecular cause of this disease. This study identified causal mutations in a 2-month-old male patient of hypomagnesemia from a consanguineous marriage. Biochemical analyses indicated the diagnosis of HSH due to primary gastrointestinal loss of magnesium. Whole exome sequencing of the trio (i.e. proband and both parents) was carried out with mean coverage of > 150×. ANNOVAR was used to annotate functional consequences of genetic variation from exome sequencing data. After variant filtering and annotation, a number of single nucleotide variants (SNVs) and 2 bp deletion at exon26:c.4402_4403delCT in TRPM6 gene were identified. This deletion which resulted in a novel frameshift mutation in exon 26 of this gene was confirmed by Sanger sequencing. With these investigations in hand, the patient was managed with magnesium sulphate. The patient remained asymptomatic and was developmentally and neurologically normal till his last follow up.

References

Dec 31, 2002·Journal of the American Society of Nephrology : JASN·Martin Konrad, Stefanie Weber
Feb 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Vladimir ChubanovThomas Gudermann
Apr 23, 2005·The Journal of Physiology·Karl P Schlingmann, Thomas Gudermann
Aug 19, 2005·Journal of the American Society of Nephrology : JASN·Karl P SchlingmannMartin Konrad
Sep 10, 2005·The Journal of Biological Chemistry·Carsten SchmitzAnne-Laure Perraud
Dec 17, 2008·Journal of the American Society of Nephrology : JASN·Stéphanie ThebaultRené J Bindels
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Jun 12, 2010·Letters in Applied Microbiology·Y J ZhangM Wang
May 22, 2013·American Journal of Nephrology·Zhen ZhaoWeibo Xia
Aug 15, 2013·European Journal of Human Genetics : EJHG·Sergio LainezJoost G Hoenderop
Dec 30, 2014·Physiological Reviews·Jeroen H F de BaaijRené J M Bindels
Sep 5, 2015·American Journal of Nephrology·Cas I van der MadeJeroen H F de Baaij
Sep 18, 2015·Nature Protocols·Hui Yang, Kai Wang
Oct 9, 2015·Magnesium Research : Official Organ of the International Society for the Development of Research on Magnesium·Jeroen H F de Baaij
Dec 4, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Kyle RettererSherri Bale
May 19, 2016·Current Opinion in Nephrology and Hypertension·Jianghui Hou
May 29, 2016·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Daan H H M VieringDetlef Bockenhauer
Nov 11, 2017·Current Nutrition and Food Science·Jan Philipp Schuchardt, Andreas Hahn
Jan 19, 2018·Kidney Diseases·Heng LiQi Qian

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.