CYP3A4 mutation causes vitamin D–dependent rickets type 3

Roizen, Jeffrey D.; Liu, Dong; O'Lear, Lauren; Javaid, M K; Shaw, Nicholas; Ebeling, Peter R.; Nguyen, Hanh H.; Rodda, Christine; Thummel, Kenneth E.; Thacher, Tom D.; Hákonarson, Hákon; Levine, Michael A.

doi:10.1172/jci98680

Cited by 88 publications

(59 citation statements)

References 23 publications

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“…Recently a publication has appeared describing two unrelated subjects with early onset of rickets for which none of the known mutations in the enzymes involved with vitamin D metabolism or VDR could be found . Both 25(OH)D and 1,25(OH) 2 D levels were low, whereas 4β,25(OH) 2 D levels were elevated.…”

Section: Cyp3a4mentioning

confidence: 99%

Vitamin D Metabolism Revised: Fall of Dogmas

Bouillon

Bikle

2019

Journal of Bone and Mineral Research

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Section: Cyp3a4mentioning

confidence: 99%

Vitamin D Metabolism Revised: Fall of Dogmas

Bouillon

Bikle

2019

Journal of Bone and Mineral Research

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“…This mutation increases CYP23A4 activity 10‐fold and has two‐fold greater activity than CYP24A1 for vitamin D inactivation. This mutation of CYP3A4 is therefore thought to be a mechanism for vitamin D deficiency …”

Section: Cyp3a4 Inactivation Of 25ohd3mentioning

confidence: 99%

The vitamin D metabolome: An update on analysis and function

Jenkinson

2019

Cell Biochemistry & Function

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Current understanding of vitamin D tends to be focussed on the measurement of the major circulating form 25‐hydroxyvitamin D3 (25OHD3) and its conversion to the active hormonal form, 1α,25‐dihydroxyvitamin D3 (1α,25(OH)2D3) via the enzyme 25‐hydroxyvitamin D‐1α‐hydroxylase (CYP27B1). However, whilst these metabolites form the endocrine backbone of vitamin D physiology, it is important to recognise that there are other metabolic and catabolic pathways that are now recognised as being crucially important to vitamin D function. These pathways include C3‐epimerization, CYP24A1 hydroxylase, CYP11A1 alternative metabolism of vitamin D3, and phase II metabolism. Endogenous metabolites beyond 25OHD3 are usually present at low endogenous levels and may only be functional in specific target tissues rather than in the general circulation. However, the technologies available to measure these metabolites have also improved, so that measurement of alternative vitamin D metabolic pathways may become more routine in the near future. The aim of this review is to provide a comprehensive overview of the various pathways of vitamin D metabolism, as well as describe the analytical techniques currently available to measure these vitamin D metabolites.

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“…WES has been the mainstay of highly successful disease‐gene discovery studies over the past decade, resulting in the identification of several genes responsible for metabolic bone disorders (e.g. WNT1 mutations as causes of osteoporosis and OI ; SFRP4 mutations in Pyle's disease ; AP2σ mutations in FHH type 3 ; PLS3 mutations in X‐linked osteoporosis ; BMP1 mutations causing increased BMD and recurrent fractures ; and CYP3A4 mutations in vitamin D‐dependent rickets, type 3 ). Disease‐targeted sequencing represents the most widely utilized NGS method in clinical practice, as it can be designed to simultaneously analyse large collections of genes (e.g.…”

Section: Clinical Approach To the Patient With A Metabolic Bone Diseasementioning

confidence: 99%

Genetic approaches to metabolic bone diseases

Hannan

Newey

Whyte

et al. 2018

Brit J Clinical Pharma

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Metabolic bone diseases comprise a diverse group of disorders characterized by alterations in skeletal homeostasis, and are often associated with abnormal circulating concentrations of calcium, phosphate or vitamin D metabolites. These diseases commonly have a genetic basis and represent either a monogenic disorder due to a germline or somatic single gene mutation, or an oligogenic or polygenic disorder that involves variants in more than one gene. Germline single gene mutations causing Mendelian diseases typically have a high penetrance, whereas the genetic variations causing oligogenic or polygenic disorders are each associated with smaller effects with additional contributions from environmental factors. Recognition of familial monogenic disorders is of clinical importance to facilitate timely investigations and management of the patient and any affected relatives. The diagnosis of monogenic metabolic bone disease requires careful clinical evaluation of the large diversity of symptoms and signs associated with these disorders. Thus, the clinician must pursue a systematic approach beginning with a detailed history and physical examination, followed by appropriate laboratory and skeletal imaging evaluations. Finally, the clinician must understand the increasing number and complexity of molecular genetic tests available to ensure their appropriate use and interpretation.

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CYP3A4 mutation causes vitamin D–dependent rickets type 3

Cited by 88 publications

References 23 publications

Vitamin D Metabolism Revised: Fall of Dogmas

Vitamin D Metabolism Revised: Fall of Dogmas

The vitamin D metabolome: An update on analysis and function

Genetic approaches to metabolic bone diseases

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