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Genotype-phenotype description of Vitamin-D Dependent Rickets 1A: CYP27B1 p.(Ala129Thr) variant induces a milder disease

dc.rights.licenseopenen_US
dc.contributor.authorMEAUX, Marie-Noelle
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorHARAMBAT, Jerome
dc.contributor.authorROTHENBUHLER, Anya
dc.contributor.authorLEGER, Juliane
dc.contributor.authorKAMENICKY, Peter
dc.contributor.authorSOSKIN, Sylvie
dc.contributor.authorBOYER, Olivia
dc.contributor.authorBOROS, Emese
dc.contributor.authorD'ANELLA, Pascal
dc.contributor.authorMIGNOT, Brigitte
dc.contributor.authorGEBHART, Maite
dc.contributor.authorVIC, Philippe
dc.contributor.authorRICHARD, Nicolas
dc.contributor.authorTHIVICHON-PRINCE, Beatrice
dc.contributor.authorFRANCOU, Bruno
dc.contributor.authorLINGLART, Agnes
dc.contributor.authorBACCHETTA, Justine
dc.contributor.authorMOLIN, Arnaud
dc.date.accessioned2022-12-16T14:14:15Z
dc.date.available2022-12-16T14:14:15Z
dc.date.issued2022-11-02
dc.identifier.issn1945-7197 (Electronic) 0021-972X (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/171553
dc.description.abstractEnINTRODUCTION: Vitamin D dependent rickets type 1A (VDDR1A) is a rare genetic disease associated with loss-of-function variations in the gene encoding the vitamin D activating enzyme 1α-hydroxylase (CYP27B1). Phenotype-genotype correlation is unclear. Long-term outcome data are lacking. The objective of this study was to describe characteristics and outcomes to search for a phenotype-genotype correlation. METHODS: We retrospectively collected clinical data, genetic features and outcomes from 24 genetically confirmed cases from 10 French centers; results are presented as median(min-max). RESULTS: Clinical symptoms at diagnosis (age 1.5(0.5-8.7) years) were mainly bone and neurological abnormalities, and laboratory data showed hypocalcemia (1.97(1.40-2.40) mmol/L), hypophosphatemia (- 3.4(-13.4-(-)0.2) SDS for age), low 25OHD and low 1,25(OH)2D3, secondary hyperparathyroidism with PTH at 6.6(1.3-13.7) times the upper limit for normal (ULN, PTH expressed as ULN to homogenize data presentation) and increased alkaline phosphatase (1968(521-7000) IU/L). Bone X-rays were abnormal in 83% of patients. We identified 17 variations (11 missense, 3 frameshift, 2 truncating and 1 acceptor splice site variations) in 19 families (homozygous state in 58% (11/19)). The partial loss-of-function variation p.(Ala129Thr) was associated with a milder phenotype: older age at diagnosis, higher serum calcium (2.26 vs 1.85 mmol/L), lower PTH (4.7 vs 7.5 ULN) and lower ALP (759 vs 2082IU/L). Patients were treated with alfacalcidol. Clinical (skeletal, neurological), biochemical and radiological outcomes were satisfactory, and complications occurred if bad adherence. CONCLUSION: Overall, our findings highlight good outcomes under substitutive treatment and the need of a closer follow-up of eyes, teeth, kidneys and blood pressure in VDDR1A.
dc.language.isoENen_US
dc.subject.enCYP27B1
dc.subject.en1-alpha hydroxylase
dc.subject.enVDDR1A
dc.subject.enRickets
dc.subject.enGenotype-phenotype
dc.title.enGenotype-phenotype description of Vitamin-D Dependent Rickets 1A: CYP27B1 p.(Ala129Thr) variant induces a milder disease
dc.title.alternativeJ Clin Endocrinol Metaben_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1210/clinem/dgac639en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed36321535en_US
bordeaux.journalJournal of Clinical Endocrinology and Metabolismen_US
bordeaux.page812-826
bordeaux.volume108
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue4
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamLEHA_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
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