Mutational analysis of patients with FGF23-related hypophosphatemic rickets

التفاصيل البيبلوغرافية
العنوان: Mutational analysis of patients with FGF23-related hypophosphatemic rickets
المؤلفون: Manabu Taguchi, Michiko Hori, Toshiro Fujita, Takashi Igarashi, T. Saito, Yuichiro Shimizu, Seiji Fukumoto, Yuka Kinoshita
المصدر: European Journal of Endocrinology. 167:165-172
بيانات النشر: Oxford University Press (OUP), 2012.
سنة النشر: 2012
مصطلحات موضوعية: Adult, Male, Fibroblast growth factor 23, medicine.medical_specialty, Adolescent, Genotype, Endocrinology, Diabetes and Metabolism, DNA Mutational Analysis, Genetic analysis, Cohort Studies, Young Adult, Exon, Endocrinology, Internal medicine, medicine, Humans, Mass Screening, Pyrophosphatases, Child, Gene, Mass screening, Genetics, Extracellular Matrix Proteins, Phosphoric Diester Hydrolases, business.industry, PHEX, Infant, Newborn, Genetic Diseases, X-Linked, General Medicine, Middle Aged, Phosphoproteins, PHEX Phosphate Regulating Neutral Endopeptidase, Fibroblast Growth Factors, Fibroblast Growth Factor-23, Hypophosphatemic Rickets, Child, Preschool, Female, Familial Hypophosphatemic Rickets, business
الوصف: ObjectiveX-linked hypophosphatemic rickets (XLHR) caused by mutations in the PHEX gene is considered to be the most frequent cause of fibroblast growth factor 23 (FGF23)-related congenital hypophosphatemic rickets. In previous studies, mutations in the PHEX gene were detected in 60–70% of patients with clinical diagnoses of XLHR. This leads to the question whether current screening methods for mutations in the PHEX gene are inadequate or whether there is a substantial number of patients with other genetic causes of hypophosphatemic rickets. We conducted a genetic analysis of patients with FGF23-related hypophosphatemic rickets to clarify their etiology and evaluate the prevalence of XLHR among this group.Design and methodsWe studied 27 patients with familial and sporadic congenital hypophosphatemic rickets in whom serum FGF23 was above 30 pg/ml using an assay for the full-length protein. Exons and exon–intron junctions of genomic DNA of causative genes for FGF23-related hypophosphatemic rickets were sequenced. PHEX mRNA from peripheral blood was analyzed in some patients.ResultsDirect sequencing of genomic DNA identified 11 novel and four known mutations in the PHEX gene. Additionally, there was a large PHEX gene deletion in one case and abnormal PHEX mRNA splicing in another. In summary, 26 patients (96%) had XLHR and one patient had autosomal recessive hypophosphatemic rickets 2.ConclusionsXLHR is by far the most prevalent cause of FGF23-related hypophosphatemic rickets. We propose that analysis of PHEX mRNA from peripheral blood would be appropriate for the first screening step in determining the etiology of FGF23-related hypophosphatemic rickets.
تدمد: 1479-683X
0804-4643
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d0770dd23accbb4ea3d5cfb6b39f5eb4
https://doi.org/10.1530/eje-12-0071
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....d0770dd23accbb4ea3d5cfb6b39f5eb4
قاعدة البيانات: OpenAIRE