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Genome sequencing identifies a large non-coding region deletion of SNX10 causing autosomal recessive osteopetrosis.

ABSTRACT: Autosomal recessive osteopetrosis (ARO) is a rare genetic disorder caused by impaired osteoclast activity. In this study, we describe a 4-year-old boy with increased bone density due to osteopetrosis, autosomal recessive 8. Using genome sequencing, we identified a large deletion in the 5'-untranslated region (UTR) of SNX10 (sorting nexin 10), where the regulatory region of this gene is located. This large deletion resulted in the absence of the SNX10 transcript and led to abnormal osteoclast activity. SNX10 is one of the nine genes known to cause ARO, shown to interact with V-ATPase (vacuolar type H( + )-ATPase), as it plays an important role in bone resorption. Our study highlights the importance of regulatory regions in the 5'-UTR of SNX10 for its expression while also demonstrating the importance of genome sequencing for detecting large deletion of the regulatory region of SNX10.

SUBMITTER: Udupa P

PROVIDER: S-EPMC10040338 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Genome sequencing identifies a large non-coding region deletion of SNX10 causing autosomal recessive osteopetrosis.

Udupa Prajna P Ghosh Debasish Kumar DK Kausthubham Neethukrishna N Shah Hitesh H Bartakke Sandip S Dalal Ashwin A Girisha Katta M KM Bhavani Gandham SriLakshmi GS

Journal of human genetics 20221216 4

Autosomal recessive osteopetrosis (ARO) is a rare genetic disorder caused by impaired osteoclast activity. In this study, we describe a 4-year-old boy with increased bone density due to osteopetrosis, autosomal recessive 8. Using genome sequencing, we identified a large deletion in the 5'-untranslated region (UTR) of SNX10 (sorting nexin 10), where the regulatory region of this gene is located. This large deletion resulted in the absence of the SNX10 transcript and led to abnormal osteoclast act ...[more]

PMID: 36526684

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Project description:Introduction and importance Autosomal recessive osteopetrosis (ARO) is a group of disease characterized by osteoclast dysfunction inhibiting bone resorption and bone turnover, with TCIRG1-associated ARO 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 mild osteopetrosis associated with TCIRG1 have been reported recently. In this study we report a rare case of non-malignant TCIRG1-associated osteopetrosis, with detail clinical characterization, genetic analysis and underwent successful total hip replacement surgery. Case presentation 24-year-old female patient came to us with limp gait, hip pain in both sides, severe stiffness. She suffered multiple fractures, bilateral hip osteoarthritis, right leg was 2 cm shorter compared with left leg. The patient had a limp gait due to severe pain and leg length discrepancy. Clinical discussion Whole Exome Sequencing, result of genetic analysis shown the patient had a compound heterozygous genotype at TCIRG1 (c.1194dup, p.Gly399ArgTer and c.334G > A, p.Gly112Arg). Total hip replacement was performed. The joint exposure and femoral canal reaming was difficult due to complete deformity of femoral head, loss of canal and high bone density. Post-operation period was uneventful; the patient rehabilitated as planned without further complication. Conclusion This is the first case of TCIRG1-associated osteopetrosis reported in Vietnam and one of the few cases of non-malignant TCIRG1-associated osteopetrosis. This case report suggests that total hip replacement is a viable option for the treatment of hip osteoarthritis in patients with mild form osteopetrosis. Highlights • This is the first case of TCIRG1-associated osteopetrosis reported in Vietnam with clinical and genetic workup.• This study detailed the surgical processes as well as the rehabilitation period of a patient with mild form of osteopetrosis.• Total hip arthroplasty is a feasible option for the treatment of hip osteoarthritis in osteopetrosis patients• High bone density, brittle/fragile bone, deformed acetabulum, narrow or sealed femoral canal leads to difficulty in surgery.

Dataset Information

Genome sequencing identifies a large non-coding region deletion of SNX10 causing autosomal recessive osteopetrosis.

Publications

Genome sequencing identifies a large non-coding region deletion of SNX10 causing autosomal recessive osteopetrosis.

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