{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:22:34Z","timestamp":1785424954749,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation to the Research Centre for Medical Genetics","award":["125040704897-7"],"award-info":[{"award-number":["125040704897-7"]}]},{"award":["125040704897-7"],"award-info":[{"award-number":["125040704897-7"]}],"id":[{"id":"https:\/\/ror.org\/03dhz7247","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Bardet\u2013Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy caused by variants in genes encoding components of the BBSome complex. Interpretation of rare variants in the BBS7 gene remains challenging, particularly for variants of uncertain significance. This study aimed to provide clinical and molecular genetic characterization of two siblings with a BBS phenotype harboring compound heterozygous variants in BBS7, including a previously undescribed missense variant. Methods: Two siblings (aged 11 and 8 years) presenting with obesity, postaxial polydactyly, retinal dystrophy, and cystic renal dysplasia were clinically evaluated. Whole-exome sequencing was performed in the proband, followed by segregation analysis within the family. Variant classification was conducted according to ACMG\/AMP guidelines, integrating allele frequency data, in silico predictions, segregation evidence, and structural modeling. Results: Two heterozygous variants in the BBS7 gene (NM_176824.3) were identified in trans: a previously reported pathogenic frameshift variant, c.1967_1968delinsC, p.(Leu656ProfsTer18), and a missense variant, c.454T&gt;C, p.(Cys152Arg), which, to the best of our knowledge, has not been previously reported in patients with Bardet\u2013Biedl syndrome. The variant was extremely rare in population databases. Structural analysis suggested steric and electrostatic disruptions, including loss of a disulfide bond. Based on ACMG\/AMP criteria, the variant was classified as likely pathogenic. Conclusions: This case supports the likely pathogenic classification of the c.454T&gt;C, p.(Cys152Arg) variant. The findings highlight the importance of integrating clinical, genetic, and structural data for the interpretation of rare variants in BBS-associated genes.<\/jats:p>","DOI":"10.3390\/genes17060614","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:17:31Z","timestamp":1780467451000},"page":"614","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and Genetic Characterization of a Russian Family with Bardet\u2013Biedl Syndrome Carrying a Previously Undescribed Missense Variant and a Recurrent Pathogenic Frameshift Variant in BBS7 Gene"],"prefix":"10.3390","volume":"17","author":[{"given":"Alexandra F.","family":"Nikolaeva","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye st., 1, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timur V.","family":"Boyko","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye st., 1, Moscow 115522, Russia"},{"name":"Faculty of Medical Biology, Department of Medical Biochemistry, Pirogov Russian National Research Medical University, Ostrovityanova st., 1, Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7765-3307","authenticated-orcid":false,"given":"Vitaly V.","family":"Kadyshev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye st., 1, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena A.","family":"Shestopalova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye st., 1, Moscow 115522, Russia"},{"name":"Moscow Clinical Scientific Center named after A. S. Loginov, 1 Novogireevskaya st., bldg. 1, Moscow 111123, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0398-7082","authenticated-orcid":false,"given":"Svetlana V.","family":"Kuznetsova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye st., 1, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9158-2522","authenticated-orcid":false,"given":"Elizabeth G.","family":"Panchenko","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye st., 1, Moscow 115522, Russia"},{"name":"Morozovskaya Children\u2019s Clinical Hospital of the Moscow City Healthcare Department, 4th Dobryninskiy Per., 1\/9, Moscow 119049, Russia"},{"name":"Department of General and Medical Genetics, Pirogov Russian National Research Medical University, Ostrovityanova st., 1, Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-4841","authenticated-orcid":false,"given":"Anatoly N.","family":"Tiulpakov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye st., 1, Moscow 115522, Russia"},{"name":"Russian Children\u2019s Clinical Hospital, Leninsky Pr., 117, Moscow 119571, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1285-9093","authenticated-orcid":false,"given":"Oxana P.","family":"Ryzhkova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye st., 1, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara O.","family":"Aripova","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Human Genomics, Academy of Sciences of the Republic of Uzbekistan, 74 Yahyo Gulyamov Street, Tashkent 100060, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4764-0841","authenticated-orcid":false,"given":"Tatyana R.","family":"Hegay","sequence":"additional","affiliation":[{"name":"Tashkent Research Centre for Medical Genetics, 74 Yahyo Gulyamov Street, Tashkent 100060, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey I.","family":"Kutsev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye st., 1, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir O.","family":"Sigin","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye st., 1, Moscow 115522, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2147\/TCRM.S338653","article-title":"Bardet-Biedl Syndrome: Current Perspectives and Clinical Outlook","volume":"19","author":"Melluso","year":"2023","journal-title":"Ther. 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