Case report of mild TCIRG1‐associated autosomal recessive osteopetrosis in Vietnam

Abstract

Autosomal recessive osteopetrosis (ARO) is a group of disease characterized by osteoclast dysfunction inhibiting bone resorption and bone turnover, with TCIRG1-associated ARO being more common leading to autosomal recessive infantile malignant osteopetrosis (OPTB1, MIM entry number # 259700). While most patients with TCIRG1-associated osteopetrosis present a malignant clinical course and shortened lifespan, a few cases of non-malignant TCIRG1-associated osteopetrosis have been reported. 24-year-old female patient came to us with limp gait, hip pain in both sides, and severe stiffness. She had suffered many fractures, bilateral hip osteoarthritis, right leg was 2 cm shorter compared with left leg. Whole Exome Sequencing was conducted, the result and subsequent Sanger's sequencing shown the patient had a compound heterozygous genotype at TCIRG1 (c.1194dup, p.Gly399ArgTer and c.334G>A, p.Gly112Arg), these two variants found were not previously reported. Sanger's sequencing revealed two other siblings whom suffer the same disorder had similar genotype to the proband; the parents were found to be heterozygous. This is the first case of TCIRG1-associated osteopetrosis reported in Vietnam and one of the few cases of nonmalignant TCIRG1-associated osteopetrosis, in which detailed clinical and genetic work-up were performed.

Structural and functional understanding of disease-associated mutations in V-ATPase subunit a1 and other isoforms

“…Therefore, MIOP patients commonly presented immune anomalies and a high incidence of infections ( Vomero et al, 2019 ). Some other reported variants in the ATP6V0A3 are compound heterozygous mutations of E266GfsX12 with E463G ( Vomero et al, 2019 ), E399RTer with E112R in a milder version of the disease ( Luong et al, 2022 ), G172D, V285Afs*204, and c.C324Wfs*X166 ( Figure 5B ; Liu et al, 2021 ).…”