{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T15:53:54Z","timestamp":1768319634654,"version":"3.49.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>Osteopetrosis is characterized by increased bone density caused by decreased osteoclasts or dysfunction of their differentiation and absorption properties, usually caused by biallelic variants of the <jats:italic>TCIRG1(OMIM:604592)<\/jats:italic>and <jats:italic>CLCN7(OMIM:602727) g<\/jats:italic>enes. Herein, the clinical, biochemical, and radiological manifestations of osteopetrosis in four Chinese children are described. Whole-exome sequencing identified compound heterozygous variants of the <jats:italic>CLCN7<\/jats:italic> and <jats:italic>TCIRG1<\/jats:italic> genes in these patients. In Patient 1, two novel variants were identified in <jats:italic>CLCN7:c.880T\u2009&amp;gt;\u2009G(p.F294V)<\/jats:italic> and <jats:italic>c.686C\u2009&amp;gt;\u2009G(p.S229X)<\/jats:italic>. Patient 2 harbored previously reported a single gene variant <jats:italic>c.643G\u2009&amp;gt;\u2009A(p.G215R) in CLCN7<\/jats:italic>. Patient 3 had a novel variant <jats:italic>c.569A\u2009&amp;gt;\u2009G(p.N190S)<\/jats:italic> and a novel frameshift variant <jats:italic>c.1113dupG(p.N372fs)<\/jats:italic> in <jats:italic>CLCN7<\/jats:italic>. Patient 4 had a frameshift variant <jats:italic>c.43delA(p.K15fs)<\/jats:italic> and variant <jats:italic>c.C1360T<\/jats:italic> in <jats:italic>TCIRG1<\/jats:italic>, resulting in the formation of a premature termination codon <jats:italic>(p.R454X)<\/jats:italic>, both of which were reported previously. Our results expand the spectrum of identified genetic variation in osteopetrosis and provide a deeper understanding of the relations between genotype and clinical characteristics of this disorder.<\/jats:p>","DOI":"10.3389\/fped.2023.1096770","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T04:40:07Z","timestamp":1678768807000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Case report: Gene mutations and clinical characteristics of four patients with 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