{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T17:26:11Z","timestamp":1773422771745,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:00:00Z","timestamp":1648166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Analyze the clinical and genetic characteristics of a rare Chinese family with Multiple synostoses syndrome and identify the causative variant with the high\u2010throughput sequencing approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The medical history investigation, physical examination, imaging examination, and audiological examination of the family members were performed. DNA samples were extracted from the family members. The candidate variant was identified by performing whole\u2010exome sequencing of the proband, then verified by Sanger sequencing in the family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The family named HBSY\u2010018 from Hubei province had 18 subjects in three generations, and six subjects were diagnosed with conductive or mixed hearing loss. Meanwhile, characteristic features including short philtrum, hemicylindrical nose, and hypoplastic alae nasi were noticed among those patients. Symptoms of proximal interdigital joint adhesion and inflexibility were found. The family was diagnosed as Multiple synostoses syndrome type 1 (SYNS1).The inheritance pattern of this family was autosomal dominant. A novel mutation in the <jats:italic>NOG<\/jats:italic> gene c.533G&gt;A was identified by performing whole\u2010exome sequencing of the proband. The substitution of cysteine encoding 178th position with tyrosine (p.Cys178Tyr) was caused by this mutation, which was conserved across species. Co\u2010segregation of disease phenotypes was demonstrated by the family verification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The family diagnosed as SYNS1 was caused by the novel mutation (c.533G&gt;A) of <jats:italic>NOG<\/jats:italic>. The combination of clinical diagnosis and molecular diagnosis had improved the understanding of this rare disease and provided a scientific basis for genetic counseling in the family.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1933","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T08:23:13Z","timestamp":1648196593000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical observation and genetic analysis of a <scp>SYNS1<\/scp> family caused by novel <scp>NOG<\/scp> gene mutation"],"prefix":"10.1002","volume":"10","author":[{"given":"Zhao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery General Hospital of Central Theater Command  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Rare Diseases Sichuan 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