AUTHOR=Chen Yu , Zhou Lina , Guan Xianmin , Wen Xianhao , Yu Jie , Dou Ying 

TITLE=Case report: Gene mutations and clinical characteristics of four patients with osteopetrosis

JOURNAL=Frontiers in Pediatrics

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2023.1096770

DOI=10.3389/fped.2023.1096770

ISSN=2296-2360

ABSTRACT=<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 <italic>TCIRG1(OMIM:604592)</italic>and <italic>CLCN7(OMIM:602727) g</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 <italic>CLCN7</italic> and <italic>TCIRG1</italic> genes in these patients. In Patient 1, two novel variants were identified in <italic>CLCN7:c.880T &gt; G(p.F294V)</italic> and <italic>c.686C &gt; G(p.S229X)</italic>. Patient 2 harbored previously reported a single gene variant <italic>c.643G &gt; A(p.G215R) in CLCN7</italic>. Patient 3 had a novel variant <italic>c.569A &gt; G(p.N190S)</italic> and a novel frameshift variant <italic>c.1113dupG(p.N372fs)</italic> in <italic>CLCN7</italic>. Patient 4 had a frameshift variant <italic>c.43delA(p.K15fs)</italic> and variant <italic>c.C1360T</italic> in <italic>TCIRG1</italic>, resulting in the formation of a premature termination codon <italic>(p.R454X)</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.</p>