ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2012
Autosomal recessive osteopetrosis: report of 41 novel mutations in the TCIRG1 gene and diagnostic implications.
Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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21 citing papers in PubMed, 46 citations in OpenAlex.
- A Novel Homozygous T-Cell Immune Regulator 1 (TCIRG1) Stop-Gain Variant Causing Malignant Infantile Osteopetrosis.Cureus · 2026Article
- Neonatal hypocalcemia and hydrocephalus as early manifestations of intermediate osteopetrosis: successful hematopoietic stem cell transplantation despite negative genetic testing: a case report.Frontiers in endocrinology · 2026Article
- Molecular Heterogeneity of Osteopetrosis in India: Report of 17 Novel Variants.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2024Article
- Autosomal Dominant Osteopetrosis (ADO) Caused by a Missense Variant in the TCIRG1 Gene.The Journal of clinical endocrinology and metabolism · 2024Article
- The Human Mutation K237_V238del in a Putative Lipid Binding Motif within the V-ATPase a2 Isoform Suggests a Molecular Mechanism Underlying Cutis Laxa.International journal of molecular sciences · 2024Article
- Outlining the Clinical Profile ofGenes · 2023Article
- Characterization of a PIP Binding Site in the N-Terminal Domain of V-ATPase a4 and Its Role in Plasma Membrane Association.International journal of molecular sciences · 2023Article
- Clinical and genetic diagnosis of autosomal dominant osteopetrosis type II in a Chinese family: A case report.World journal of clinical cases · 2023Article
- Pediatric patient with a bilateral Salter-Harris II fracture and slipped capital femoral epiphysis secondary to autosomal recessive osteopetrosis.Orthopadie (Heidelberg, Germany) · 2022Article
- Unusual Cortical Phenotype After Hematopoietic Stem Cell Transplantation in a Patient With Osteopetrosis.JBMR plus · 2022Article
- Genetic analysis of osteopetrosis in Pakistani families identifies novel and known sequence variants.BMC medical genomics · 2021Article
- Clinical and molecular characterization of five Chinese patients with autosomal recessive osteopetrosis.Molecular genetics & genomic medicine · 2021Article
- Two novel mutations in TCIRG1 induced infantile malignant osteopetrosis: a case report.BMC pediatrics · 2021Article
- The V-ATPaseInternational journal of molecular sciences · 2021Review
- Rab GTPases in Osteoclastic Bone Resorption and Autophagy.International journal of molecular sciences · 2020Review
- Complex Heterozygous Mutation in the T-cell Immune Regulator 1 Gene Associated with Severe Ocular Characteristics of Osteopetrosis in an Infant.Chinese medical journal · 2018Article
- Genetics of Osteopetrosis.Current osteoporosis reports · 2018Review
- Cervical spine fractures in osteopetrosis: a case report and review of the literature.Journal of biomedical research · 2018Article
- Ophthalmic phenotype of TCIRG1 gene mutations in Chinese infantile malignant osteopetrosis.BMJ open ophthalmology · 2018Article
- As little as needed: the extraordinary case of a mild recessive osteopetrosis owing to a novel splicing hypomorphic mutation in the TCIRG1 gene.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2014Article
Corrections and comments
- Erratum issuedIacono, N L [corrected to Lo Iacono, N]
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledHere we report 41 novel mutations in the TCIRG1 gene that is responsible for the disease in more than 50% of ARO patients. The characterisation of mutations in this gene might be useful in the process of drug design for osteoporosis treatment.
introductionAutosomal recessive osteopetrosis (ARO) is a genetically heterogeneous disorder due to reduced bone resorption by osteoclasts. In this process, a crucial role is played by the proton pump V-ATPase. Biallelic mutations in the TCIRG1 gene, encoding for the a3 subunit of this pump, are responsible for more than one half of ARO patients.
methodsPatients with a clinical diagnosis of ARO have been collected for 7 years and mutation analysis of the TCIRG1 gene was performed using direct DNA sequencing of PCR-amplified exons according to both a standard protocol and a modified one.
resultsWe report here 41 novel mutations identified in 67 unpublished patients, all with biallelic mutations. In particular, we describe two novel large genomic deletions and two splice site mutations in the 5' UTR of the TCIRG1 gene, in patients previously classified as mono-allelic.
conclusionsOur data highlights the importance of two large genomic deletions and mutations in the 5' UTR with respect to patient management and, more critically, to prenatal diagnosis. With the present work, we strongly contribute to the molecular dissection of TCIRG1-deficient ARO and identify several protein residues which are fundamental for proton pump function and could thus be the target of future drugs designed to inhibit osteoclast resorptive activity.
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