{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T20:33:15Z","timestamp":1788294795617,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:00:00Z","timestamp":1653004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012542","name":"Sichuan Province Science and Technology Support Program","doi-asserted-by":"publisher","award":["2021JDRC0045 2021JDRC0169 2021YJ0472 2021YFS0164 2022YFS0202"],"award-info":[{"award-number":["2021JDRC0045 2021JDRC0169 2021YJ0472 2021YFS0164 2022YFS0202"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Brachydactyly type A1 (BDA1) is an autosomal dominant inherited disease characterized by the shortness\/absence of the middle phalanges, which can be induced by mutations in the Indian hedgehog gene (<jats:italic>IHH<\/jats:italic>). Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by joint destruction, synovitis, and the presence of autoantibodies. In this study, the proband was diagnosed with both BDA1 and RA. We performed whole-exome sequencing in a four-generation Chinese family to investigate their inherited causal mutation to BDA1. A novel in-frame insertion variant in <jats:italic>IHH<\/jats:italic>: NM_002,181.4: c.383_415dup\/p.(R128_H138dup) was identified in the BDA1 pedigree. This insertion of 11 amino acids was located in the highly conserved amino-terminal signaling domain of <jats:italic>IHH<\/jats:italic> and co-segregated with the disease status. This adds one to the total number of different <jats:italic>IHH<\/jats:italic> mutations found to cause BDA1. Moreover, we found a potential causal germline variant in <jats:italic>CRY1<\/jats:italic> for a molecular biomarker of RA (i.e., a high level of anti-cyclic citrullinated peptide). Collectively, we identified novel variants in <jats:italic>IHH<\/jats:italic> for inherited BDA1, which highlights the important role of this gene in phalange development.<\/jats:p>","DOI":"10.3389\/fgene.2022.814786","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T08:38:53Z","timestamp":1653035933000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case Report: Brachydactyly Type A1 Induced by a Novel Variant of in-Frame Insertion in the IHH Gene"],"prefix":"10.3389","volume":"13","author":[{"given":"Feier","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyang","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qibing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5693","DOI":"10.18632\/aging.102958","article-title":"Indian Hedgehog Regulates Senescence in Bone Marrow-Derived Mesenchymal Stem Cell through Modulation of ROS\/mTOR\/4EBP1, p70S6K1\/2 Pathway","volume":"12","author":"Al-Azab","year":"2020","journal-title":"Aging"},{"key":"B2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1684\/ecn.2018.0405","article-title":"TL1A Mediates Fibroblast-like Synoviocytes Migration and Indian Hedgehog Signaling Pathway via TNFR2 in Patients with Rheumatoid Arthritis","volume":"29","author":"Al-Azab","year":"2018","journal-title":"Eur. 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