A Novel G102E Mutation of CYP27B1 in a Large Family with Vitamin D-Dependent Rickets Type 1

Alzahrani, Ali S.; Zou, Minjing; Baitei, Essa Y.; Alshaikh, Omalkhaire M.; Al-Rijjal, Roua A.; Meyer, Brian F.; Shi, Yufei

doi:10.1210/jc.2009-2278

Cited by 51 publications

(34 citation statements)

References 22 publications

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“…VDDR-1A is an autosomal recessive disorder due to an inactivating mutation in the CYP27B1 gene on chromosome 12q14 (1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21). The CYP27B1 gene encodes 25(OH) D-1-α-hydroxylase which catalyzes the hormonally regulated, rate limiting step in the bioactivation of vitamin D (1,2,3,4).…”

Section: Discussionmentioning

confidence: 99%

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A Case of Vitamin D-Dependent Rickets Type 1A with a Novel Mutation in the Uzbek Population

Özcabı¹,

Bucak²,

Jaferova³

et al. 2016

Jcrpe

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Vitamin D-dependent rickets type 1A (VDDR-1A) (Online Mendelian Inheritance in Man #264700) is a rare, autosomal recessively inherited disorder due to inactivating mutations in CYP27B1. It is characterized by early onset of rickets with hypocalcemia. We aimed to describe the clinical and laboratory findings in a VDDR-1A case and to report a novel homozygote truncating mutation NM_000785.3 c.403C>T (p.Q135*) in CYP27B1 which to our knowledge is the first described mutation in the Uzbek population. The patient was admitted with tetany at the age of 12 months. He was a healthy Uzbek boy until 9 months of age when he had a seizure due to hypocalcemia. Vitamin D treatment was given orally in Turkmenistan (no data available for dose and duration). The patient was the product of a consanguineous marriage. His brother had died with hypocalcemia and pneumonia. At physical examination, anthropometric measurements were within normal limits; he had caput quadratum, enlarged wrists, and carpopedal spasm. Blood calcium, phosphorus, alkaline phosphatase, and parathormone (PTH) levels were 5.9 mg/dL, 3.5 mg/dL, 987 IU/L, and 182.8 pg/mL (12-72), respectively. Radiological findings included cupping and fraying of the radial and ulnar metaphyses. Renal ultrasound revealed nephrocalcinosis (grade 1). Despite high serum PTH and 25-hydroxyvitamin D3 levels, 1,25-dihydroxyvitamin D3 level was low, suggesting a diagnosis of VDDR-1A. The patient was treated with calcium carbonate and calcitriol. DNA sequencing revealed a novel homozygous mutation of NM_000785.3 c.403C>T (p.Q135*) in CYP27B1. VDDR-1A is a rare disorder which needs to be considered even in countries where nutritional vitamin D deficiency is still common.

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Section: Discussionmentioning

confidence: 99%

“…The CYP27B1 gene is mapped on chromosome 12q14 (4). In different ethnic groups, several mutations (homozygous or compound heterozygous) have been identified in patients with VDDR-1A (3,5,7,8,9,10,11,g,13,14,15,16,17,18,19,20,21). In some ethnic groups, certain mutations are more frequent (2,8,14,20).…”

Section: Introductionmentioning

confidence: 99%

A Case of Vitamin D-Dependent Rickets Type 1A with a Novel Mutation in the Uzbek Population

Özcabı¹,

Bucak²,

Jaferova³

et al. 2016

Jcrpe

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“…Le rachitisme « pseudo-carentiel » de type I Cette affection se transmet sur le mode autosomique récessif et résulte d'une mutation inactivatrice du gène CYP27B1 codant le cytochrome P450 spécifique de la 25(OH)D 1-hydroxylase. Plus de 30 mutations du gène CYP27B1 ont été décrites à ce jour [13].…”

Section: Les Rachitismes Vitamino-résistantsunclassified

Maladies génétiques avec troubles du métabolisme phosphocalcique

Marcelli¹

2012

Revue du Rhumatisme Monographies

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“…It is approximately 5 Kb and is composed of nine exons13). Furthermore, several laboratories have characterized mutations in the 1α-hydroxylase gene in patients with VDDR-I14-23). VDDR-I is characterized by failure to thrive, muscle weakness, hypocalcemia, secondary hyperparathyroidism, and the bony changes of rickets3).…”

Section: Vitamin D 1α-hydroxylasementioning

confidence: 99%

Vitamin D dependent rickets type I

Kim

2011

Korean J Pediatr

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Vitamin D is present in two forms, ergocalciferol (vitamin D2) produced by plants and cholecalciferol (vitamin D3) produced by animal tissues or by the action of ultraviolet light on 7-dehydrocholesterol in human skin. Both forms of vitamin D are biologically inactive pro-hormones that must undergo sequential hydroxylations in the liver and the kidney before they can bind to and activate the vitamin D receptor. The hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D], plays an essential role in calcium and phosphate metabolism, bone growth, and cellular differentiation. Renal synthesis of 1,25(OH)2D from its endogenous precursor, 25-hydroxyvitamin D (25OHD), is the rate-limiting and is catalyzed by the 1α-hydroxylase. Vitamin D dependent rickets type I (VDDR-I), also referred to as vitamin D 1α-hydroxylase deficiency or pseudovitamin D deficiency rickets, is an autosomal recessive disorder characterized clinically by hypotonia, muscle weakness, growth failure, hypocalcemic seizures in early infancy, and radiographic findings of rickets. Characteristic laboratory features are hypocalcemia, increased serum concentrations of parathyroid hormone (PTH), and low or undetectable serum concentrations of 1,25(OH)2D despite normal or increased concentrations of 25OHD. Recent advances have showed in the cloning of the human 1α-hydroxylase and revealed mutations in its gene that cause VDDR-I. This review presents the biology of vitamin D, and 1α-hydroxylase mutations with clinical findings.

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A Novel G102E Mutation of CYP27B1 in a Large Family with Vitamin D-Dependent Rickets Type 1

Abstract: A novel mutation in the CYP27B1 gene was found in patients with VDDR-I. This mutation resulted in a significant reduction in 1alpha-hydroxylase activity. The residual enzymatic activity may account for the mild phenotype presentation in some affected members.

Cited by 51 publications

References 22 publications

A Case of Vitamin D-Dependent Rickets Type 1A with a Novel Mutation in the Uzbek Population

A Case of Vitamin D-Dependent Rickets Type 1A with a Novel Mutation in the Uzbek Population

Maladies génétiques avec troubles du métabolisme phosphocalcique

Vitamin D dependent rickets type I

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