Hereditary vitamin D-resistant rickets in Lebanese patients: the p.R391S and p.H397P variants have different phenotypes
-
Rabih Andary
,
Theresa Farhat
und
Georges Nemer
Abstract:
Background:
Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disorder caused by mutations in the vitamin D receptor (VDR) gene. Variable phenotypes have been associated with these mutations, and some of these were linked to the effects they have on the interacting partners of VDR, mainly the retinoic X receptor (RXR).
Methods:
We examined four patients with HVDRR from three unrelated Lebanese families. All parents were consanguineous with normal phenotype. We used Sanger sequencing to identify mutations in the coding exons of VDR.
Results:
Two homozygous mutations (p.R391S and p.H397P), both in exon 9 of the VDR gene, were identified. Phenotype/genotype association was not possible even for the same mutation. Alopecia was seen only with the p.R391S mutation. Despite a comparable rachitic bone disease, the patients showed different responsiveness to large doses of alfacalcidol (1-α-hydroxy vitamin D3) supplementation.
Conclusions:
This is the first report of VDR mutations in Lebanon with promising clinical outcomes despite the severity of the phenotypes.
Acknowledgments
We thank the patients and their families for their contribution to this research. Special thanks to Mrs Inaam El-Rassy for Sanger sequencing at the Molecular Core Facilities at the faculty of Medicine at the American University of Beirut.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This study was partially funded by a grant from Union Pharmaceutique d’Orient s.a.l. (Ms Norma Audi).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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©2017 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Editorial
- Pediatric endocrinology is pediatrics is public health
- Original Articles
- Total body fat, abdominal fat, body fat distribution and surrogate markers for health related to adipocyte fatty acid-binding protein (FABP4) in children
- Vitamin D supplementation, the metabolic syndrome and oxidative stress in obese children
- Vitamin D status in Egyptian children with type 1 diabetes and the role of vitamin D replacement in glycemic control
- Cross-sectional analysis of universal vitamin D supplementation in former East Germany during the first year of life
- Ethnicity and incidence of congenital hypothyroidism in the capital of Macedonia
- Changes of thyroid hormonal status in patients receiving ketogenic diet due to intractable epilepsy
- Leptin and adiponectin levels in discordant dichorionic twins at 72 hours of age-associations with anthropometric parameters and insulin resistance
- Analysis of growth hormone receptor gene expression in tall and short stature children
- Clinical features of girls with short stature among inv (9), Turner (45, X) and control individuals
- Hereditary vitamin D-resistant rickets in Lebanese patients: the p.R391S and p.H397P variants have different phenotypes
- Associations between obesity, adverse behavioral patterns and cardiovascular risk factors among adolescent inhabitants of a Greek island
- Increase of body mass index (BMI) from 1.5 to 3 years of age augments the degree of insulin resistance corresponding to BMI at 12 years of age
- Case Reports
- The variable clinical phenotype of three patients with hepatic glycogen synthase deficiency
- Molecular defects identified by whole exome sequencing in a child with atypical mucopolysaccharidosis IIIB
- Clinical presentation and treatment response to diazoxide in two siblings with congenital hyperinsulinism as a result of a novel compound heterozygous ABCC8 missense mutation
- Cushing’s syndrome in infancy due to ectopic ACTH secretion by a sacro-coccygeal teratoma
- Letters to the Editor
- Growth-hormone deficiency in mitochondrial disorders
- Response to Growth hormone deficiency in mitochondrial disorders
Artikel in diesem Heft
- Frontmatter
- Editorial
- Pediatric endocrinology is pediatrics is public health
- Original Articles
- Total body fat, abdominal fat, body fat distribution and surrogate markers for health related to adipocyte fatty acid-binding protein (FABP4) in children
- Vitamin D supplementation, the metabolic syndrome and oxidative stress in obese children
- Vitamin D status in Egyptian children with type 1 diabetes and the role of vitamin D replacement in glycemic control
- Cross-sectional analysis of universal vitamin D supplementation in former East Germany during the first year of life
- Ethnicity and incidence of congenital hypothyroidism in the capital of Macedonia
- Changes of thyroid hormonal status in patients receiving ketogenic diet due to intractable epilepsy
- Leptin and adiponectin levels in discordant dichorionic twins at 72 hours of age-associations with anthropometric parameters and insulin resistance
- Analysis of growth hormone receptor gene expression in tall and short stature children
- Clinical features of girls with short stature among inv (9), Turner (45, X) and control individuals
- Hereditary vitamin D-resistant rickets in Lebanese patients: the p.R391S and p.H397P variants have different phenotypes
- Associations between obesity, adverse behavioral patterns and cardiovascular risk factors among adolescent inhabitants of a Greek island
- Increase of body mass index (BMI) from 1.5 to 3 years of age augments the degree of insulin resistance corresponding to BMI at 12 years of age
- Case Reports
- The variable clinical phenotype of three patients with hepatic glycogen synthase deficiency
- Molecular defects identified by whole exome sequencing in a child with atypical mucopolysaccharidosis IIIB
- Clinical presentation and treatment response to diazoxide in two siblings with congenital hyperinsulinism as a result of a novel compound heterozygous ABCC8 missense mutation
- Cushing’s syndrome in infancy due to ectopic ACTH secretion by a sacro-coccygeal teratoma
- Letters to the Editor
- Growth-hormone deficiency in mitochondrial disorders
- Response to Growth hormone deficiency in mitochondrial disorders
