Genetic testing for calcium sensing receptor (CaSR) (R319)

Background information

Identification of pathogenic variants in the CaSR gene in relation to the clinical/biochemical presentation can assist in directing patient management and whether surgical intervention is required.

The CaSR plays an essential role in maintaining mineral ion homeostasis. Pathogenic variants in the CaSR gene can cause the following disorders of calcium homeostasis:

Familial benign hypocalciuric hypercalcaemia (FBHH/FHH1) OMIM +145980

Familial isolated hyperparathyroidism (FIHP) OMIM +145000

Autosomal dominant hypocalcaemia (ADH1) - OMIM 146200: an autosomal dominant condition characterised by gain of function/activating mutations. Clinically variable from asymptomatic to neonatal/childhood seizures.

Neonatal or neonatal severe hyperparathyroidism (NHPT or NSHPT) OMIM 239200: clinically variable but may present with extreme hypercalcaemia, failure to thrive and skeletal defects during infancy. Autosomal recessive and dominant inheritance reported. Information as below.

Testing strategy

Clinically affected probands

R319.1 - single gene analysis for small variants in the CaSR gene

Targeted analysis for known / previously reported familial variants:

• Diagnostic confirmation in individuals at risk of inheriting a previously reported familial pathogenic variant and clinically suspected of having the familial condition (R240)
• Testing in clinically unaffected family members at risk of inheriting a previously reported familial pathogenic variant (R242)
• Segregation studies in affected family members to aid variant interpretation (R375)
• Prenatal diagnosis is not typically requested

Sample requirements and referral information

All referrals should ideally be accompanied by a completed pre-referral form.

Clinical guidance and advice is available to referring consultants from:

Professor Rajesh Thakker, Professor of Medicine
OCDEM, Churchill Hospital

Email: rajesh.thakker@ndm.ox.ac.uk

Requesting specialties

• Endocrinology
• Clinical Genetics

Specimen requirements and referring samples

Price list for non NHSE referrals (pdf)