Exome sequencing identifies a novel frameshift variant causing hypomagnesemia with secondary hypocalcemia
M Kamran Azim1,2, Aisha Mehnaz3, Javeria Z Ahmed3
1International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan. Kamran.azim@jinnah.edu.
CEN Case Reports
|August 26, 2018
Summary
Hypomagnesemia with secondary hypocalcemia (HSH) is a rare genetic disorder. This study identified a novel TRPM6 gene mutation causing HSH in an infant, successfully managed with magnesium sulfate.
Area of Science:
- Genetics
- Molecular Biology
- Pediatrics
Background:
- Hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal-recessive disorder.
- Mutations in the TRPM6 gene are the established cause of HSH.
- TRPM6 encodes an epithelial magnesium channel crucial for magnesium homeostasis.
Observation:
- A 2-month-old male infant from a consanguineous marriage presented with hypomagnesemia.
- Biochemical analyses confirmed HSH due to primary gastrointestinal magnesium loss.
- Whole exome sequencing was performed on the proband and parents.
Findings:
- A novel 2 bp deletion (c.4402_4403delCT) in exon 26 of the TRPM6 gene was identified.
- This deletion resulted in a frameshift mutation, confirmed by Sanger sequencing.
- The identified mutation was causal for HSH in the patient.
Implications:
- This finding expands the mutational spectrum of the TRPM6 gene in HSH.
- Early diagnosis and management with magnesium sulfate are crucial for HSH patients.
- The patient remained asymptomatic and showed normal development, highlighting effective treatment outcomes.
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