{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T03:51:14Z","timestamp":1777348274189,"version":"3.51.4"},"reference-count":57,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"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","award":["075-15-2021-1058"],"award-info":[{"award-number":["075-15-2021-1058"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypophosphatasia (HPP) is a rare inherited disorder characterized by the decreased activity of tissue-nonspecific alkaline phosphatase (TNSALP), caused by mutations in the ALPL gene. The aim of this study was to conduct differential diagnostics in HPP patients using whole-exome sequencing (WES). The medical records of HPP patients and the genetic testing of the ALPL gene were reviewed. Seven patients were recruited and underwent WES using the Illumina or MGI sequencing platforms. All of the exome samples were matched onto a GRCh38.p13 reference genome assembly by using the Genome Analysis ToolKit (GATK) and the BWA MEM read aligner. We present the clinical and molecular findings of the seven patients referred for genetic analyses due to a clinical and biochemical suspicion of HPP. In two patients out of three (with identified heterozygous variants in the ALPL gene), we also identified c.682T&gt;A in exon 3 of the WNT10A gene and c.3470del in exon 23 of the SMC1A gene variants for the first time. In four patients, variants in the ALPL gene were not detected, but WES allowed us to identify for the first time rare variants (c.5651A&gt;C in exon 36 of the TRIO gene, c.880T&gt;G in exon 6 of the TRPV4 gene, c.32078-1G&gt;T in intron 159 of the TTN gene, c.47720_47721del in exon 235 of the TTN gene, and c.1946G&gt;A in exon 15 of the SLC5A1 gene) and to conduct differential diagnostics with HPP. Using WES, for the first time, we demonstrate the possibility of early differential diagnostics in HPP patients with other rare genetic diseases.<\/jats:p>","DOI":"10.3390\/ijms252111728","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T09:57:36Z","timestamp":1730368656000},"page":"11728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Benefits of Whole-Exome Sequencing in the Differential Diagnosis of Hypophosphatasia"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0091-2224","authenticated-orcid":false,"given":"Oleg S.","family":"Glotov","sequence":"first","affiliation":[{"name":"Department of Genomic Medicine, D. O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint Petersburg, Russia"},{"name":"Department of Experimental Medical Virology, Molecular Genetics and Biobanking of Pediatric Research and Clinical Center for Infectious Diseases, 197022 Saint Petersburg, Russia"},{"name":"CerbaLab Ltd., 199106 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalya A.","family":"Zhuchenko","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, N.V. Sklifosovsky ICM, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria S.","family":"Balashova","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, D. O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint Petersburg, Russia"},{"name":"Department of Medical Genetics, N.V. Sklifosovsky ICM, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra N.","family":"Raspopova","sequence":"additional","affiliation":[{"name":"CerbaLab Ltd., 199106 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria V.","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, D. O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint Petersburg, Russia"},{"name":"Department of Experimental Medical Virology, Molecular Genetics and Biobanking of Pediatric Research and Clinical Center for Infectious Diseases, 197022 Saint Petersburg, Russia"},{"name":"CerbaLab Ltd., 199106 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2464-7370","authenticated-orcid":false,"given":"Alexandr N.","family":"Chernov","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, D. O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint Petersburg, Russia"},{"name":"Department of General Pathology and Pathological Physiology, Institute of Experimental Medicine, 197022 Saint Petersburg, Russia"},{"name":"Department of Biological Chemistry, Federal State Budgetary Educational Institution of Higher Education Saint Petersburg State Pediatric Medical University of the Ministry of Health of Russia, 194100 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6128-4738","authenticated-orcid":false,"given":"Iana V.","family":"Chuiko","sequence":"additional","affiliation":[{"name":"Faculty of Bioengineering and Bioinformatics, Moscow State University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lavrentii G.","family":"Danilov","sequence":"additional","affiliation":[{"name":"CerbaLab Ltd., 199106 Saint Petersburg, Russia"},{"name":"Department of Genetics and Biotechnology, Saint-Petersburg State University, 199034 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyudmila D.","family":"Morozova","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, N.V. Sklifosovsky ICM, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7465-4504","authenticated-orcid":false,"given":"Andrey S.","family":"Glotov","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, D. O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint Petersburg, Russia"},{"name":"Department of Genetics and Biotechnology, Saint-Petersburg State University, 199034 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1001\/archpedi.1948.02030020840003","article-title":"Hypophosphatasia; a new developmental anomaly","volume":"75","author":"Rathbun","year":"1948","journal-title":"Am. J. Dis. 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