Novel Vitamin D Receptor Mutations in Hereditary Vitamin D Resistant Rickets in Chinese

September 2015 in “ PLoS ONE ”

Lee‐Moay Lim, Xuan Zhao, Mei‐Chyn Chao, Jer-Ming Chang, Wei‐Chiao Chang, Hung‐Ying Kao, Daw‐Yang Hwang, Hung‐Chun Chen

vitamin D receptor VDR gene 1,25-dihydroxyvitamin D hypocalcemia hypophosphatemia rickets alopecia transactivation dimerization RXR

Studysummary This case report documents a female toddler with novel compound heterozygous mutations in the VDR gene causing hereditary 1,25-dihydroxyvitamin D-resistant rickets, expanding the known mutation spectrum for this disease. Our plain-language summary of this paper — not a Tressless recommendation.

The study described a case of a female toddler with hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR), characterized by severe rickets, hypocalcemia, and hypophosphatemia, but notably without alopecia. Genetic analysis identified novel compound heterozygous mutations in the VDR gene: p.M4I and p.H229Q. The p.M4I mutation, in combination with FOKI-F, eliminated both translation start sites of the VDR protein, while the p.H229Q mutation resulted in significantly reduced VDR transactivation activity despite normal dimerization with RXR. This report expanded the known mutation spectrum of HVDRR and highlighted the first case where a benign variant p.M4I, along with a common p.M1T polymorphism, contributed to a pathogenic allele.

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research Mutations in the Vitamin D Receptor and Hereditary Vitamin D-Resistant Rickets

107 citations , March 2014 in “BoneKEy Reports”

This abstract reviews hereditary vitamin D-resistant rickets, a rare genetic condition causing severe early childhood rickets, and reports no new results; effective treatment typically requires high doses of calcium to address hypocalcemia and secondary hyperparathyroidism.

research The Hair Cycle and Vitamin D Receptor

50 citations , October 2011 in “Archives of Biochemistry and Biophysics”

This study found that while calcium can substitute for the Vitamin D receptor in maintaining epidermal keratinocyte differentiation, it cannot compensate for hair follicle dysfunction caused by the absence of the receptor.

research Hereditary Vitamin D-Resistant Rickets (HVDRR) Owing to a Heterozygous Mutation in the Vitamin D Receptor

37 citations , August 2011 in “Journal of Bone and Mineral Research”

This study reported a case of hereditary vitamin D–resistant rickets caused by a single heterozygous missense mutation in the VDR gene, showing dominant-negative effects and reduced response to 1,25-dihydroxyvitamin D3.

research The Role of Vitamin D Receptor Mutations in the Development of Alopecia

109 citations , June 2011 in “Molecular and Cellular Endocrinology”

Vitamin D receptor mutations can cause alopecia by affecting hair growth genes.

research Genetic Disorders and Defects in Vitamin D Action

151 citations , June 2010 in “Endocrinology and metabolism clinics of North America”

This article compares two rare genetic diseases, vitamin D-dependent rickets type 1 and type 2, focusing on their similar presentations of hypocalcemia and rickets in infancy, but reports no new clinical results.

research Two New Unrelated Cases of Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets with Alopecia Resulting from the Same Novel Nonsense Mutation in the Vitamin D Receptor Gene

36 citations , January 2010 in “Journal of Pediatric Endocrinology and Metabolism”

This study identified a novel nonsense mutation in the VDR gene in two patients with hereditary vitamin D resistant rickets and alopecia, leading to resistance to 1,25-dihydroxyvitamin D3.

research Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets With Alopecia Resulting From a Novel Missense Mutation in the DNA-Binding Domain of the Vitamin D Receptor

50 citations , September 2009 in “Molecular Genetics and Metabolism”

This study identified a novel V26M mutation in the vitamin D receptor as the cause of hereditary vitamin D resistant rickets in a patient, characterized by severe rickets and an unusual pattern of alopecia.