It Remains Unknown Whether Filaggrin Gene Mutations Evolved to Increase Cutaneous Synthesis of Vitamin D

Focussing on the UV induced cutaneous synthesis of vitamin D, this review gives an update on the relevance of the VDES and of UV radiation for the management of psoriasis and other inflammatory skin diseases.

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Vitamin D 1α-Hydroxylase Gene Mutations in Patients with 1α-Hydroxylase Deficiency

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-2664 ◽

2007 ◽

Vol 92 (8) ◽

pp. 3177-3182 ◽

Cited By ~ 69

Author(s):

Chan Jong Kim ◽

Larry E. Kaplan ◽

Farzana Perwad ◽

Ningwu Huang ◽

Amita Sharma ◽

...

Keyword(s):

Vitamin D ◽

Direct Sequencing ◽

Gene Mutations ◽

Splice Site Mutation ◽

Autosomal Recessive Disorder ◽

The United States ◽

Site Mutation ◽

Hydroxylase Deficiency ◽

Exon 2 ◽

Hydroxylase Gene

Abstract Context: Vitamin D 1α-hydroxylase deficiency, also known as vitamin D-dependent rickets type 1, is an autosomal recessive disorder characterized by the early onset of rickets with hypocalcemia and is caused by mutations of the 25-hydroxyvitamin D 1α-hydroxylase (1α-hydroxylase, CYP27B1) gene. The human gene encoding the 1α-hydroxylase is 5 kb in length, located on chromosome 12, and comprises nine exons and eight introns. We previously isolated the human 1α-hydroxylase cDNA and gene and identified 19 different mutations in 25 patients with 1α-hydroxylase deficiency. Objectives, Patients, and Methods: We analyzed the 1α-hydroxylase gene of 10 patients, five from Korea, two from the United States, and one each from Argentina, Denmark, and Morocco, all from nonconsanguineous families. Each had clinical and radiographic features of rickets, hypocalcemia, and low serum concentrations of 1,25-dihydroxyvitamin D3. Results: Direct sequencing identified the responsible 1α-hydroxylase gene mutations in 19 of 20 alleles. Four novel and four known mutations were identified. The new mutations included a nonsense mutation in exon 6, substitution of adenine for guanine (2561G→A) creating a stop signal at codon 328; deletion of adenine in exon 9 (3922delA) causing a frameshift; substitution of thymine for cytosine in exon 2 (1031C→T) causing the amino acid change P112L; and a splice site mutation, substitution of adenine for guanine in the first nucleotide of intron 7 (IVS7+1 G→A) causing a frameshift. Conclusions: Mutations in the 1α-hydroxylase gene previously were identified in 44 patients, to which we add 10 more. The studies show a strong correlation between 1α-hydroxylase mutations and the clinical findings of 1α-hydroxylase deficiency.

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Novel CYP27B1 Gene Mutations in Patients with Vitamin D-Dependent Rickets Type 1A

PLoS ONE ◽

10.1371/journal.pone.0131376 ◽

2015 ◽

Vol 10 (7) ◽

pp. e0131376 ◽

Cited By ~ 17

Author(s):

Korcan Demir ◽

Walaa E. Kattan ◽

Minjing Zou ◽

Erdem Durmaz ◽

Huda BinEssa ◽

...

Keyword(s):

Vitamin D ◽

Gene Mutations

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Controversies regarding the relation between solar radiation, cutaneous synthesis of vitamin D and the development of malignant melanoma

Romanian Journal of Infectious Diseases ◽

10.37897/rjid.2015.1.4 ◽

2015 ◽

Vol 18 (1) ◽

pp. 24-29

Author(s):

Corina-Daniela Ene ◽

◽

Amalia-Elena Anghel ◽

Alina Muşetescu ◽

Ilinca Nicolae ◽

...

Keyword(s):

Vitamin D ◽

Skin Cancer ◽

Malignant Melanoma ◽

Cellular Proliferation ◽

Experimental Studies ◽

Sun Exposure ◽

Serum Levels ◽

The Body ◽

Melanoma Metastasis ◽

Cutaneous Synthesis

The relation between sun exposure, vitamin D synthesis and skin cancer is a complex one. Radiations from the sun stimulate the cutaneous vitamin D synthesis, one way, and promote the development of the skin cancer on the other way. A lot of epidemiologic and experimental studies revealed contradictory results regarding the relation between vitamin D and malignant melanoma. The vitamin D deficiency, accurate biochemical indicator of the vitamin D status in the body, could be implicated in promoting metastasis of the malignant melanoma by activation of the cellular proliferation, stimulation of the neutrophils chemotaxis and promoting angiogenesis. Identification of therapeutic strategies to normalise serum levels of the 25-OH vitamin D3 could represent useful tools in preventing melanoma metastasis.

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Disorders of bone mineralization—osteomalacia

10.1093/med/9780199642489.003.0146 ◽

2013 ◽

Author(s):

Deepak R. Jadon ◽

Tehseen Ahmed ◽

Ashok K. Bhalla

Keyword(s):

Vitamin D ◽

Bone Mineralization ◽

Bone Biopsy ◽

Gene Mutations ◽

Sun Exposure ◽

Phosphate Deficiency ◽

Skeletal Deformity ◽

Bone Scans ◽

Metabolizing Enzyme ◽

Biochemical Assessment

Disorders of bone mineralization cause rickets in children and osteomalacia in adults. Both remain common in developing countries. Incidence in Western countries had declined since the fortification of foodstuffs, but appears to be increasing again. Calcium and inorganic phosphate are the key precursors for bone mineralization and growth. The commonest aetiology of osteomalacia is vitamin D deficiency, primarily due to low dietary intake and inadequate sun exposure. In the last decade gene mutations have been identified that are responsible for inherited rickets and osteomalacia, particularly those that result in phosphate deficiency, hypophosphatasia, and vitamin D receptor or metabolizing enzyme mutations. Additionally, the pathogenesis of tumour-induced osteomalacia is becoming better understood. Osteomalacia may present as bone pain and tenderness, muscle pain and weakness, and skeletal deformity or fracture. Key investigations include biochemical assessment and plain radiographs. Radioisotope bone scans and bone biopsy may be considered in selected cases. Differential diagnoses include osteoporosis, seronegative arthritides, and localized soft tissue disorders. Treatment, guided by the underlying aetiology, aims to reduce symptoms, fracture risk, bone deformity and sequelae. Vitamin D deficient patients require vitamin D and calcium replacement.

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Seasonal Vitamin D Intake In Quebec Preschoolers

Canadian Journal of Dietetic Practice and Research ◽

10.3148/65.4.2004.174 ◽

2004 ◽

Vol 65 (4) ◽

pp. 174-179 ◽

Cited By ~ 2

Author(s):

Doris Gagné ◽

Marc Rhainds ◽

Isabelle Galibois

Keyword(s):

Vitamin D ◽

Food Frequency Questionnaire ◽

Adequate Intake ◽

Food Frequency ◽

Vitamin D Intake ◽

Multivitamin Supplement ◽

Seasonal Factors ◽

Food Recall ◽

Supplement Intake ◽

Cutaneous Synthesis

As a number of seasonal factors affect cutaneous synthesis of vitamin D, especially in young children, our objective was to verify if winter and summer vitamin D intakes in Quebec preschoolers reach the adequate intake of 5 µg/day. A three-month retrospective food frequency questionnaire and a 24-hour food recall were used with parents of 98 children (mean age 56 months) in summer and of 72 of these children (mean age 65 months) in winter. To ensure completeness of data, vitamin D content of foods not covered in the Canadian Nutrient File was taken from other sources. According to the food frequency questionnaire, total vitamin D intakes were 9.7 ± 4.3 g/day in summer and 11.6 ± 4.8 g/day in winter. Only 10% of children in summer and 7% in winter had an intake below 5 µg/day. The 24-hour food recall vitamin D intake estimate was lower (summer 7.0 ± 3.8 µg/day, winter 7.2 ± 4.2 µg/day). This difference could be partly due to a discrepancy in the estimation of multivitamin supplement intake. However, according to both estimates, vitamin D intakes appeared generally adequate in this sample of Quebec preschoolers.

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Factors that influence the cutaneous synthesis and dietary sources of vitamin D

Archives of Biochemistry and Biophysics ◽

10.1016/j.abb.2006.12.017 ◽

2007 ◽

Vol 460 (2) ◽

pp. 213-217 ◽

Cited By ~ 299

Author(s):

Tai C. Chen ◽

Farhad Chimeh ◽

Zhiren Lu ◽

Jeffrey Mathieu ◽

Kelly S. Person ◽

...

Keyword(s):

Vitamin D ◽

Cutaneous Synthesis

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Idiopathic infantile hypercalcemia: mutations in SLC34A1 and CYP24A1 in two siblings and fathers

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0169 ◽

2020 ◽

Vol 33 (10) ◽

pp. 1353-1358

Author(s):

Ayla Güven ◽

Martin Konrad ◽

Karl P. Schlingmann

Keyword(s):

Vitamin D ◽

Stop Codon ◽

Gene Mutations ◽

Splice Site Mutation ◽

Heterozygous Mutation ◽

High Dose ◽

Loss Of Function ◽

Site Mutation ◽

Medullary Nephrocalcinosis ◽

Idiopathic Infantile Hypercalcemia

AbstractObjectivesBoth CYP24A1 and SLC34A1 gene mutations are responsible for idiopathic infantile hypercalcemia, whereas loss-of-function mutations in CYP24A1 (25-OH-vitamin D-24-hydroxylase) lead to a defect in the inactivation of active 1.25(OH)2D; mutations in SLC34A1 encoding renal sodium phosphate cotransporter NaPi-IIa lead to primary renal phosphate wasting combined with an inappropriate activation of vitamin D. The presence of mutations in both genes has not been reported in the same patient until today.Case presentationHypercalcemia was incidentally detected when a 13-month-old boy was being examined for urinary tract infection. After 21 months, hypercalcemia was detected in his six-month-old sister. High dose of vitamin D was not given to both siblings. Both of them also had hypophosphatemia and decreased tubular phosphate reabsorption. Intensive hydration, furosemide and oral phosphorus treatment were given. Bilateral medullary nephrocalcinosis was detected in both siblings and their father. Serum Ca and P levels were within normal limits at follow-up in both siblings. Siblings and their parents all carry a homozygous stop codon mutation (p.R466*) in CYP24A1. Interestingly, both siblings and the father also have a heterozygous splice-site mutation (IVS6(+1)G>A) in SLC34A1. The father has nephrocalcinosis.ConclusionsA biallelic loss-of-function mutation in the CYP24A1 gene was identified as responsible for hypercalcemia, hypercalciuria and nephrocalcinosis. In addition, a heterozygous mutation in the SLC34A1 gene, although not being the main pathogenic factor, might contribute to the severe phenotype of both patients.

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Disorders of bone mineralization—osteomalacia

Oxford Textbook of Rheumatology ◽

10.1093/med/9780199642489.003.0146_update_002 ◽

2013 ◽

pp. 1252-1258

Author(s):

Deepak R. Jadon ◽

Tehseen Ahmed ◽

Ashok K. Bhalla

Keyword(s):

Vitamin D ◽

Bone Mineralization ◽

Bone Biopsy ◽

Gene Mutations ◽

Sun Exposure ◽

Phosphate Deficiency ◽

Skeletal Deformity ◽

Bone Scans ◽

Metabolizing Enzyme ◽

Biochemical Assessment

Disorders of bone mineralization cause rickets in children and osteomalacia in adults. Both remain common in developing countries. Incidence in Western countries had declined since the fortification of foodstuffs, but appears to be increasing again. Calcium and inorganic phosphate are the key precursors for bone mineralization and growth. The commonest aetiology of osteomalacia is vitamin D deficiency, primarily due to low dietary intake and inadequate sun exposure. In the last decade gene mutations have been identified that are responsible for inherited rickets and osteomalacia, particularly those that result in phosphate deficiency, hypophosphatasia, and vitamin D receptor or metabolizing enzyme mutations. Additionally, the pathogenesis of tumour-induced osteomalacia is becoming better understood. Osteomalacia may present as bone pain and tenderness, muscle pain and weakness, and skeletal deformity or fracture. Key investigations include biochemical assessment and plain radiographs. Radioisotope bone scans and bone biopsy may be considered in selected cases. Differential diagnoses include osteoporosis, seronegative arthritides, and localized soft tissue disorders. Treatment, guided by the underlying aetiology, aims to reduce symptoms, fracture risk, bone deformity and sequelae. Vitamin D deficient patients require vitamin D and calcium replacement.

Download Full-text