{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T14:05:56Z","timestamp":1767276356206,"version":"3.41.2"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003395","name":"Shanghai Municipal Education Commission","doi-asserted-by":"publisher","award":["18SG14"],"award-info":[{"award-number":["18SG14"]}],"id":[{"id":"10.13039\/501100003395","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Osteopetrosis is characterized by increased bone density and bone marrow cavity stenosis due to a decrease in the number of osteoclasts or the dysfunction of their differentiation and absorption properties usually caused by biallelic variants of the <jats:italic>TCIRG1<\/jats:italic> and <jats:italic>CLCN7<\/jats:italic>\u00a0genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we describe five Chinese children who presented with anemia, thrombocytopenia, hepatosplenomegaly, repeated infections, and increased bone density. Whole\u2010exome sequencing identified five compound heterozygous variants of the <jats:italic>CLCN7<\/jats:italic> and <jats:italic>TCIRG1<\/jats:italic>\u00a0genes in these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patient 1\u00a0had a novel variant c.1555C&gt;T (p.L519F) and a previously reported pathogenic variant c.2299C&gt;T (p.R767W) in <jats:italic>CLCN7<\/jats:italic>. Patient 2\u00a0harbored a novel missense variant (c.1025T&gt;C; p.L342P) and a novel splicing variant (c.286\u20109G&gt;A) in <jats:italic>CLCN7<\/jats:italic>. Patients 3A and 3B from one family displayed the same compound heterozygous <jats:italic>TCIRG1<\/jats:italic> variant, including a novel frameshift variant (c.1370del; p.T457Tfs*71) and a novel splicing variant (c.1554+2T&gt;C). In Patient 4, two novel variants were identified in the <jats:italic>TCIRG1<\/jats:italic>\u00a0gene: c.676G&gt;T; p.E226* and c.1191del; p.P398Sfs*5. Patient 5\u00a0harbored two known pathogenic variants, c.909C&gt;A (p.Y303*) and c.2008C&gt;T (p.R670*), in <jats:italic>TCIRG1<\/jats:italic>. Analysis of the products obtained from the reverse transcription\u2010polymerase chain reaction revealed that the c.286\u20109G&gt;A variant in <jats:italic>CLCN7<\/jats:italic> of patient 2\u00a0leads to intron 3 retention, resulting in the formation of a premature termination codon (p.E95Vfs*8). These five patients were eventually diagnosed with autosomal recessive osteopetrosis, and the three children with <jats:italic>TCIRG1<\/jats:italic> variants received hematopoietic stem cell transplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results expand the spectrum of variation of genes related to osteopetrosis and deepen the understanding of the relationship between the genotype and clinical characteristics of osteopetrosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1815","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T08:35:07Z","timestamp":1632213307000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clinical and molecular characterization of five Chinese patients with autosomal recessive 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