{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:05:40Z","timestamp":1772118340071,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Alstr\u00f6m syndrome (AS) is a rare recessive disorder characterised by diabetes, obesity, insulin resistance (IR), and visual and hearing impairments. Mutations in the\n                      <jats:italic>ALMS1<\/jats:italic>\n                      gene have been identified as the causative agents of AS. This study aimed to explore the relationship between rare\n                      <jats:italic>ALMS1<\/jats:italic>\n                      variants and clinical features in Chinese patients with early\u2010onset type 2 diabetes (age at diagnosis \u226440\u00a0years; EOD).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>ALMS1<\/jats:italic>\n                      gene sequencing was performed in 611 Chinese individuals with EOD, 36 with postprandial hyperinsulinemia, and 47 with pre\u2010diabetes and fasting IR. In\u2010silico prediction algorithm and the American College of Medical Genetics Guidelines (ACMG) were used to evaluate the deleteriousness and pathogenicity of the variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sixty\u2010two rare\n                      <jats:italic>ALMS1<\/jats:italic>\n                      variants (frequency &lt;0.005) were identified in 82 patients with EOD. Nineteen variants were predicted to be deleterious (pD). Patients with EOD carrying pD variants had higher fasting C\u2010peptide, postprandial C\u2010peptide, and HOMA2\u2010IR levels than those without variants. The frequency of\n                      <jats:italic>ALMS1<\/jats:italic>\n                      pD variants in the subgroup with more insulin\u2010resistant EOD was higher than that in other EOD subgroups. Two patients with EOD, obesity, and IR who carried one heterozygous pathogenic\/likely pathogenic rare variant of\n                      <jats:italic>ALMS1<\/jats:italic>\n                      according to ACMG were identified. Moreover, rare heterozygous pD variants of\n                      <jats:italic>ALMS1<\/jats:italic>\n                      were found in participants from cohorts of postprandial hyperinsulinemia as well as in pre\u2010diabetes with fasting IR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>ALMS1<\/jats:italic>\n                      rare pD variants are enriched in the populations with significant IR, which is a major hallmark of diabetes pathogenesis. Accordingly, our exploratory study provides insights and hypotheses for further studies of gene function.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dmrr.3788","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T08:10:16Z","timestamp":1711613416000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Overburden of rare ALMS1 deleterious variants in Chinese early\u2010onset type 2 diabetes with severe insulin resistance"],"prefix":"10.1002","volume":"40","author":[{"given":"Simin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Peking University People's Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqian","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Peking University People's Hospital  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