A novel CLCN7 mutation resulting in a most severe form of autosomal recessive osteopetrosis.

Osteopetrosis is a bone disease characterized by osteoclast failure and impaired bone resorption. Genetically, it is classified in three forms with autosomal recessive (ARO), autosomal dominant, and intermediate autosomal recessive inheritance, respectively. Some ARO forms are also associated with primary neurodegeneration, retinal atrophy, and lysosomal storage, which are caused by CLCN7 and OSTM1 gene mutations. Herein, we present a unique consanguineous family with a 26-month-old child with osteopetrosis, neurodegeneration, retinal atrophy, and tubulopathy. Direct sequencing of the CLCN7 gene showed a novel homozygous R561Q variant in the patient. Both healthy parents were heterozygous for this amino acid substitution indicating autosomal recessive inheritance. The same homozygous nucleotide transition was found prenatally in a second child and the pregnancy was terminated at 17th week of gestation. A full autopsy was performed to the fetus, which confirmed the presence of osteopetrosis, thereby indicating that the variant observed indeed represents the disease-causing mutation. This is the first report of ARO associated with a novel recessive R561Q variant in CLCN7 gene, in which prenatal diagnosis was made.