A novel CASR mutation (p.Glu757Lys) causing autosomal dominant hypocalcaemia type 1

Area of Science:

• Genetics
• Endocrinology
• Calcium Metabolism

Background:

• Autosomal dominant hypocalcaemia type 1 (ADH1) is a rare genetic disorder.
• It is characterized by low serum calcium and parathyroid hormone (PTH) levels.
• ADH1 results from activating mutations in the Calcium-Sensing Receptor (CASR) gene.

Purpose of the Study:

• To describe a novel heterozygous missense mutation in CASR causing ADH1 in an Australian family.
• To highlight the clinical manifestations and genetic basis of ADH1.
• To emphasize the importance of genetic diagnosis for patient management and family screening.

Main Methods:

• Clinical case description of an Australian family with ADH1.
• Identification and characterization of a novel CASR mutation.
• Review of clinical symptoms, biochemical parameters, and family history.

Main Results:

• A novel heterozygous missense mutation in CASR was identified in the affected family.
• Affected individuals presented with mild neuromuscular symptoms like paraesthesia and carpopedal spasm.
• Basal ganglia calcification was observed in three out of four affected family members.

Conclusions:

• Genetic confirmation of CASR mutations is crucial for diagnosing ADH1.
• Early diagnosis enables proper management, including calcium and calcitriol supplementation for symptomatic patients.
• Genetic counseling and screening of family members are essential for managing this rare familial disorder.