Funding outcome

Autosomal Dominant Hypocalcemia (ADH) is a childhood disorder resulting in low blood calcium and abnormally low parathyroid hormone (PTH) hormone, which functions to increase blood calcium. A 9-year old girl with seizures had low blood calcium, low PTH and increased urinary calcium excretion. She was treated with supplemental vitamin D and calcium. She has no mutation in the genes known to cause ADH and her parents and brother do not have ADH. So we sequenced the parents' and children's DNA which revealed she has a mutation in the FAM111A gene. FAM111A mutations cause Kenny Caffey syndrome and Gracile bone disease. Both are characterized by low blood calcium, low PTH, short stature and bony abnormalities. Our patient does not have short stature or bony abnormalities but her other characteristics are consistent with a mutation in the FAM111A gene causing her disease. In order to confirm our hypothesis, that mutations in FAM111A cause a range of diseases that all include low blood calcium levels, we generated a mutant mouse carrying the same mutation as our patient. The objective is to determine if this mutation in the mouse induces low blood calcium and PTH. FAM111A mutant mice will be placed in special cages to collect urine and blood before they are euthanized. Using a variety of techniques, the collected urine and blood will then be examined and compared to control mice which do not have the mutation. The effect of this mutation will also be examined in kidney and parathyroid cells. This work will explain the cause of our patient's disorder by demonstrating that mutations in FAM111A cause ADH. The mutant mice will also be valuable tools on which to test new therapies.