Vitamin D receptor genotype in hypophosphatemic rickets as a predictor of growth and response to treatment.

Context: Treatment of X-linked hypophosphatemic rickets improves bone mineralization and bone deformities, but its effect on skeletal growth is highly variable.

Objective: Genetic variants in the promoter region of the vitamin D receptor (VDR) gene may explain the response to treatment because this receptor mediates vitamin D action.

Design: We studied the VDR promoter haplotype structure in a large cohort of 91 patients with hypophosphatemic rickets including 62 patients receiving 1alpha-hydroxyvitamin D3 derivatives and phosphates from early childhood on.

A maternal epimutation of GNAS leads to Albright osteodystrophy and parathyroid hormone resistance.

Context: Pseudohypoparathyroidism (PHP) type Ia is a rare maternally transmitted disease due to maternal loss-of-function mutations of GNAS, the gene encoding Galphas, the alpha-stimulatory subunit of the G protein. Affected individuals display hormonal resistance (mainly PTH and TSH resistance) and Albright hereditary osteodystrophy. PHP type Ib (PHP-Ib), usually defined by isolated renal resistance to PTH and sometimes mild TSH resistance, is due to a maternal loss of GNAS exon A/B methylation, leading to decreased Galphas expression in specific tissues.

Vitamin D-resistant rickets and type 1 diabetes in a child with compound heterozygous mutations of the vitamin D receptor (L263R and R391S): dissociated responses of the CYP-24 and rel-B promoters to 1,25-dihydroxyvitamin D3.

Unlabelled: We report here the first association between vitamin D-resistant rickets, alopecia, and type 1 diabetes in a child with compound heterozygous mutations in the VDR gene. Transfection studies suggest dissociated effects of VDR gene mutations on the regulation of genes involved in vitamin D metabolism and dendritic cell maturation.

Introduction: Whereas vitamin D may play a role in the immune tolerance process, no patient has been reported to associate hereditary vitamin D-resistant rickets (HVDRR) and an autoimmune disease, and no attempt has been made to delineate the outcome of mutations of the vitamin D receptor (VDR) on the transcription of genes controlling immune tolerance.

Dental abnormalities in patients with familial hypophosphatemic vitamin D-resistant rickets: prevention by early treatment with 1-hydroxyvitamin D.

Objective: To evaluate the dental effects of 1-hydroxylated vitamin D3 treatment in patients with familial hypophosphatemic vitamin D-resistant rickets. Study design Forty-eight children and adult patients were included in the study; 16 had received no treatment or phosphate supplements with vitamin D/25-(OH) D3 before puberty. The 32 younger ones had received phosphate supplements with 1alpha-(OH)D3 from infancy.

Making the unit of insulin: standards, clinical work, and industry, 1920-1925.

The standardization of insulin is generally considered by historians to have been a process conducted by physiologists under the direction of Henry Dale. This article shows that it actually involved many actors and began with the earliest administration to patients in Canada and the United States. During this first phase, the drug company Eli Lilly also contributed actively to the standardization, under the scientific direction of George Clowes.