An overview of CYP27B1 enzyme mutation and management: A case report and review of the literature

Zamanfar, Daniel; Ghazaiean, Mobin

doi:10.1002/ccr3.7007

Cited by 3 publications

(1 citation statement)

References 38 publications

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“…In this context, several studies demonstrated that mutations in three CYP genes ( CYP7A1 , CYP7B1 , and CYP27A1 ) affect bile acid synthesis and cholesterol homeostasis, with different phenotypes leading to metabolic pathologies [ 46 , 47 , 48 , 49 , 50 , 51 ]. Defects in CYPs 2R1 and 27B1, involved in the conversion of vitamin D into its physiologically active form, are genetic causes of rickets [ 52 , 53 , 54 , 55 ]. Deficiency in the retinoic acid-metabolizing enzymes from the CYP26 family is associated with skeletal and craniofacial anomalies [ 56 , 57 ].…”

Section: The Cyp Enzyme Complexmentioning

confidence: 99%

Pleiotropy of Progesterone Receptor Membrane Component 1 in Modulation of Cytochrome P450 Activity

Barata,

Rueff,

Kranendonk

et al. 2024

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Progesterone receptor membrane component 1 (PGRMC1) is one of few proteins that have been recently described as direct modulators of the activity of human cytochrome P450 enzymes (CYP)s. These enzymes form a superfamily of membrane-bound hemoproteins that metabolize a wide variety of physiological, dietary, environmental, and pharmacological compounds. Modulation of CYP activity impacts the detoxification of xenobiotics as well as endogenous pathways such as steroid and fatty acid metabolism, thus playing a central role in homeostasis. This review is focused on nine main topics that include the most relevant aspects of past and current PGRMC1 research, focusing on its role in CYP-mediated drug metabolism. Firstly, a general overview of the main aspects of xenobiotic metabolism is presented (I), followed by an overview of the role of the CYP enzymatic complex (IIa), a section on human disorders associated with defects in CYP enzyme complex activity (IIb), and a brief account of cytochrome b5 (cyt b5)’s effect on CYP activity (IIc). Subsequently, we present a background overview of the history of the molecular characterization of PGRMC1 (III), regarding its structure, expression, and intracellular location (IIIa), and its heme-binding capability and dimerization (IIIb). The next section reflects the different effects PGRMC1 may have on CYP activity (IV), presenting a description of studies on the direct effects on CYP activity (IVa), and a summary of pathways in which PGRMC1’s involvement may indirectly affect CYP activity (IVb). The last section of the review is focused on the current challenges of research on the effect of PGRMC1 on CYP activity (V), presenting some future perspectives of research in the field (VI).

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Section: The Cyp Enzyme Complexmentioning

confidence: 99%

Pleiotropy of Progesterone Receptor Membrane Component 1 in Modulation of Cytochrome P450 Activity

Barata,

Rueff,

Kranendonk

et al. 2024

JoX

View full text Add to dashboard Cite

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Siblings with vitamin D‐dependent rickets type 1A: Importance of genetic testing and a review of genotype–phenotype correlations

Wang,

Shanmugasundaram,

Cooney

et al. 2024

American J of Med Genetics Pt A

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Vitamin D‐dependent rickets type 1A (VDDR1A) is a rare condition caused by biallelic pathogenic variants in CYP27B1, which encodes 25‐hydroxyvitamin D3‐1‐α‐hydroxylase. Inadequate activity of this enzyme results in deficient 1α‐hydroxylation of inactive 25‐hydroxyvitamin D to biologically active 1,25‐dihydroxyvitamin D, with consequent adverse effects on calcium and phosphate metabolism. A female child was clinically diagnosed at 18 months old with hypophosphatemic rickets based on phenotype and biochemical testing, with neither parent affected. A subsequent affected male sibling led to the reconsideration of the diagnosis. Exome sequencing showed a homozygous CYP27B1 c.1040T>A (p.Ile347Asn) variant for both children. No variants were found in genes associated with hypophosphatemic rickets. A review of published cases of VDDR1A with homozygous CYP27B1 variants indicates variable clinical presentation, lack of genotype–phenotype correlation, and low serum phosphate at diagnosis in most cases. These findings emphasize the clinical importance of molecular testing as part of the diagnostic evaluation for cases of non‐nutritional rickets.

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Compound Heterozygous Variants of CYP27B1 Causing Autosomal Recessive Vitamin D-Dependent Rickets Type 1A in an Indian Child

Kakkad,

Oza

2024

Indian Pediatrics Case Reports

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Background: Vitamin D-dependent rickets Type 1A (VDDR-1A) is a rare cause of rickets occurring due to variants of CYP27B1 responsible for encoding enzyme 1ά hydroxylase. Clinical Description: We report a 17-months-old girl who presented to us with clinical and radiological features of rickets. The biochemistry investigations suggestive of low calcium, low phosphorous, markedly elevated alkaline phosphatase and parathyroid hormone, high-normal 25 hydroxy Vitamin D level and inappropriately normal 1,25 dihydroxy Vitamin D levels, and no response to oral calcium and Vitamin D supplementation, prompted the diagnosis of VDDR-1A, which was proven genetically with a novel compound heterozygous variant. Management and Outcome: She was treated with oral calcitriol 1.5 μg/day and oral elemental calcium at 500 mg/day; after which at the 3-month follow-up, improvement in clinical, biochemical, and radiological features was observed. Conclusion: Following a clinical diagnosis of VDDR, genetic analysis is preferable to identify the variant and hence understand the genotype–phenotype correlation.

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An overview of CYP27B1 enzyme mutation and management: A case report and review of the literature

Cited by 3 publications

References 38 publications

Pleiotropy of Progesterone Receptor Membrane Component 1 in Modulation of Cytochrome P450 Activity

Pleiotropy of Progesterone Receptor Membrane Component 1 in Modulation of Cytochrome P450 Activity

Siblings with vitamin D‐dependent rickets type 1A: Importance of genetic testing and a review of genotype–phenotype correlations

Compound Heterozygous Variants of CYP27B1 Causing Autosomal Recessive Vitamin D-Dependent Rickets Type 1A in an Indian Child

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