Genotype, Phenotype Characteristics and Long-Term Follow-Up of Patients with Vitamin D-Dependent Rickets Type IA: A Nationwide Multi-Centre Retrospective Cross-Sectional Study
Cayir, Atilla, Demirbilek, Huseyin, Turkyilmaz, Ayberk, Turan, Serap, Bereket, Abdullah, Darendeliler, Feyza, Ozbek, Mehmet Nuri, Koca, Serkan Bilge, Unal, Edip, Okdemir, Deniz, Esen, Ihsan, Eren, Erdal, Yildirim, Ruken, Cetinkaya, Semra, Sahin, Kadriye Cansu, Anik, Ahmet, Donmez, Ayse Sena, Ozturk, Ayse Pinar, Bayramoglu, Elvan, Buyukinan, Muammer, Gurbuz, Fatih, Demir, Korcan, Kilinc, Suna, Buyukyilmaz, Gonul, Kaygusuz, Sare Betul, Celmeli, Gamze, Eklioglu, Beray Selver, Acar, Sezer, Dursun, Fatma, Turan, Ihsan, Ozkaya, Beyhan, Kurnaz, Erdal, Baran, Riza Taner, Ozkan, Behzat
Introduction: Vitamin D-dependent rickets type IA (VDDR1A) is an autosomal recessive disorder characterized by defects in the biosynthesis of its active form 1,25-dihydroxyvitamin D due to mutations in the CYP27B1 gene, which encodes for 1 alpha-hydroxylase. The present study aimed to evaluate the clinical characteristics, molecular genetic aetiology, and long-term outcomes of a large nationwide cohort of children with VDDR1A from Turkey. Methods: In this multi-centre retrospective cross-sectional study, we collected clinical characteristics, laboratory features, molecular genetic analysis results, and long-term follow-up of a nationwide cohort of patients with VDDR1A using a web-based research network, CEDD-NET, for paediatric endocrinology research. Results: In total, 118 patients (57 F, 61 M) with VDDR1A were recruited. The median age of the diagnosis was 1.7 years (0.2-18.3 years). The most common presenting complaints were skeletal deformity (n = 61), short stature (n = 45), and delay in walking (n = 42). The most common mutation was a splice-donor-site mutation (c.195+2T>G) (n = 42), followed by a 7-bp duplication 1319-1325dupCCCACCC (Phe443Profs*24) (n = 25), and two missense mutations p.K192E (c.574A>G) (n = 17) and c.1474C>T (p.R492W) (n = 12). The novel c.195+2T>C and c.1215_1215+2delTGTinsCGA splice-site and c.1144C>A missense variants were firstly described in our cohort. Conclusion: The most common four mutations accounted for the underlying aetiology of VDDR1A in approximately 81% of the cohort, indicating Turkey may serve as a mutational hotspot or exhibit a founder effect for these variants. Our large cohort's results suggested no clear and clinically meaningful phenotype-genotype relationship in VDDR1A
- Journal
- HORMONE RESEARCH IN PAEDIATRICS
- Year
- 2025
- ISSN
- 1663-2818
- eISSN
- 1663-2826
- DOI
- 10.1159/000546497
- WoS UID
- WOS:001546322900001