Abstract
Introduction Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare
disorder caused by perturbation in renal reabsorption of magnesium and calcium. Biallelic
pathogenic variants either in gene CLDN16 or CLDN19 are responsible for molecular defects. Most patients with CLDN19 variants have been associated with ocular involvements (FHHNCOI).
Patient and Methods We had a pediatric patient with hypercalciuric hypomagnesemia and bilateral chorioretinal
atrophy. Metabolic profiling and radiology examinations were performed, in addition
to whole exome sequencing (WES) used for detection of the causative variant.
Results Analysis of WES revealed a homozygous c.223G > A (p.G75S) variant in CLDN19 . MutationTaster and Combined Annotation-Dependent Depletion support its deleterious
effect and SHERLOC's criteria put it in pathogenic category. This variant is previously
reported in compound heterozygous state with other known pathogenic variant. As far
as we know, it is the first report of this variant in homozygous state.
Conclusion The variant found in our patient is pathogenic and compatible with FHHNCOI characteristics.
WES is an advantageous tool in molecular diagnosis and finding genetic pathology of
this disease. In line with other reports, ocular abnormalities are variable in patients
with CLDN19 mutations, and chronic kidney disease and retinal damages must be considered in this
group.
Keywords WES - hypomagnesemia - hypercalciuria - chorioretinal atrophy - CLDN19
