Genotype-phenotype description of Vitamin-D Dependent Rickets 1A: CYP27B1 p.(Ala129Thr) variant induces a milder disease
dc.rights.license | open | en_US |
dc.contributor.author | MEAUX, Marie-Noelle | |
hal.structure.identifier | Bordeaux population health [BPH] | |
dc.contributor.author | HARAMBAT, Jerome | |
dc.contributor.author | ROTHENBUHLER, Anya | |
dc.contributor.author | LEGER, Juliane | |
dc.contributor.author | KAMENICKY, Peter | |
dc.contributor.author | SOSKIN, Sylvie | |
dc.contributor.author | BOYER, Olivia | |
dc.contributor.author | BOROS, Emese | |
dc.contributor.author | D'ANELLA, Pascal | |
dc.contributor.author | MIGNOT, Brigitte | |
dc.contributor.author | GEBHART, Maite | |
dc.contributor.author | VIC, Philippe | |
dc.contributor.author | RICHARD, Nicolas | |
dc.contributor.author | THIVICHON-PRINCE, Beatrice | |
dc.contributor.author | FRANCOU, Bruno | |
dc.contributor.author | LINGLART, Agnes | |
dc.contributor.author | BACCHETTA, Justine | |
dc.contributor.author | MOLIN, Arnaud | |
dc.date.accessioned | 2022-12-16T14:14:15Z | |
dc.date.available | 2022-12-16T14:14:15Z | |
dc.date.issued | 2022-11-02 | |
dc.identifier.issn | 1945-7197 (Electronic) 0021-972X (Linking) | en_US |
dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/171553 | |
dc.description.abstractEn | INTRODUCTION: 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.iso | EN | en_US |
dc.subject.en | CYP27B1 | |
dc.subject.en | 1-alpha hydroxylase | |
dc.subject.en | VDDR1A | |
dc.subject.en | Rickets | |
dc.subject.en | Genotype-phenotype | |
dc.title.en | Genotype-phenotype description of Vitamin-D Dependent Rickets 1A: CYP27B1 p.(Ala129Thr) variant induces a milder disease | |
dc.title.alternative | J Clin Endocrinol Metab | en_US |
dc.type | Article de revue | en_US |
dc.identifier.doi | 10.1210/clinem/dgac639 | en_US |
dc.subject.hal | Sciences du Vivant [q-bio]/Santé publique et épidémiologie | en_US |
dc.identifier.pubmed | 36321535 | en_US |
bordeaux.journal | Journal of Clinical Endocrinology and Metabolism | en_US |
bordeaux.page | 812-826 | |
bordeaux.volume | 108 | |
bordeaux.hal.laboratories | Bordeaux Population Health Research Center (BPH) - UMR 1219 | en_US |
bordeaux.issue | 4 | |
bordeaux.institution | Université de Bordeaux | en_US |
bordeaux.institution | INSERM | en_US |
bordeaux.team | LEHA_BPH | en_US |
bordeaux.peerReviewed | oui | en_US |
bordeaux.inpress | non | en_US |
hal.export | false | |
dc.rights.cc | Pas de Licence CC | en_US |
bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal%20of%20Clinical%20Endocrinology%20and%20Metabolism&rft.date=2022-11-02&rft.volume=108&rft.issue=4&rft.spage=812-826&rft.epage=812-826&rft.eissn=1945-7197%20(Electronic)%200021-972X%20(Linking)&rft.issn=1945-7197%20(Electronic)%200021-972X%20(Linking)&rft.au=MEAUX,%20Marie-Noelle&HARAMBAT,%20Jerome&ROTHENBUHLER,%20Anya&LEGER,%20Juliane&KAMENICKY,%20Peter&rft.genre=article |
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