{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:04:25Z","timestamp":1785535465945,"version":"3.56.0"},"reference-count":20,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T00:00:00Z","timestamp":1728604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Department of the Hospital General of Mexico \u201cDr. Eduardo Liceaga\u201d General","award":["DI\/23\/501\/04\/32"],"award-info":[{"award-number":["DI\/23\/501\/04\/32"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Vitamin D-dependent rickets type 1A (VDDR1A) is a rare autosomal recessive disorder caused by pathogenic variants in the CYP27B1 gene, typically characterized by growth failure, rickets, leg bowing, fracture, seizures, hyperparathyroidism, hypocalcemia, high-alkaline phosphatase, high or normal 25(OH)D3, and low 1,25(OH)2D3. Methods: We studied two siblings in a Mexican family with an atypical form of VDDR1A. In addition to the typical features of VDDR1A, the proband showed cafe au lait spots, small teeth, and grayish sclera, with hypophosphatemia, normocalcemia, and normal 25(OH)D3; the proband\u2019s brother showed grayish sclera. The proband underwent next generation sequencing. Sanger sequencing was performed in the proband, his brother, the parents, and 100 healthy controls validate the detected variant. Results: Both brothers presented with a recurrent variant NM_000785.3; c.1319_1325dupCCCACCC and a novel nonsense variant NM_000785.3; c.227G&gt;A in the CYP27B1 gene. Conclusions: Calcitriol treatment had a better response in proband\u00b4s younger brother. We describe the first Mexican family with an atypical form of VDDR1A associated with a novel nonsense variant, the results contribute to the phenotypic spectrum and increase the pool of pathogenic variants in CYP27B1. Data suggest that nonsense-truncating variants play a significant role in the severity of VDDR1A.<\/jats:p>","DOI":"10.3390\/diseases12100248","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T03:53:47Z","timestamp":1728618827000},"page":"248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Compound Nonsense Variant in CYP27B1 Causes an Atypical Form of Vitamin D-Dependent Rickets Type 1A: A Case Report of Two Siblings in a Mexican Family"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0324-7351","authenticated-orcid":false,"given":"Jaime","family":"Toral L\u00f3pez","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Centro Medico ISSEMYM Ecatepec, Ecatepec 55000, M\u00e9xico State, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Candia Tenopala","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Centro Medico ISSEMYM Ecatepec, Ecatepec 55000, M\u00e9xico State, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alix Daniela","family":"Reyes Mosqueda","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Therapeutic Imaging, Centro Medico ISSEMYM Ecatepec, Ecatepec 55000, M\u00e9xico State, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel \u00c1ngel","family":"Fonseca S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Investigation, Hospital General de M\u00e9xico \u201cDr. Eduardo Liceaga\u201d, M\u00e9xico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luz Mar\u00eda","family":"Gonz\u00e1lez Huerta","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Section of Investigation, Department of Genetic, Hospital General de M\u00e9xico \u201cDr. Eduardo Liceaga\u201d, M\u00e9xico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1056\/NEJM197310182891601","article-title":"Pathogenesis of hereditary vitamin-D-dependent rickets. 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