Vitamin D-dependent rickets (VDDR) is a group of genetic disorders characterized by early-onset rickets due to deficiency of active vitamin D or a failure to respond to activated vitamin D. VDDR is divided into several subtypes according to the corresponding causative genes. Here we described a new type of autosomal dominant VDDR in a Chinese pedigree. The proband and his mother had severe bone malformations, dentin abnormalities, and lower serum 25 hydroxyvitamin D3 (25[OH]D3) and phosphate levels. The proband slightly responded to a high dose of vitamin D3 instead of a daily low dose of vitamin D3. Whole-exome sequencing, bioinformatic analysis, PCR, and Sanger sequencing identified a nonsense mutation in CYP4A22 (c.900delG). The overexpressed wild-type CYP4A22 mainly localized in endoplasmic reticulum and Golgi apparatus, and synthesized 25(OH)D3 in HepG2 cells. The overexpressed CYP4A22 mutant increased the expression of CYP2R1 and produced little 25(OH)D3 with vitamin D3 supplementation, which was reduced by CYP2R1 siRNA treatment. We concluded that CYP4A22 functions as a new kind of 25-hydroxylases for vitamin D3. Loss-of-function mutations in CYP4A22 lead to a new type of VDDR type 1 (VDDR1C). CYP2R1 and CYP4A22 may have some genetic compensation responding to nonsense-mediated mRNA decay effect of each other.
A nonsense mutation in CYP4A22 was found in a Chinese pedigree with vitamin D–dependent rickets and low serum phosphate. CYP4A22 localizes in endoplasmic reticulum and Golgi apparatus, and processes 25-hydroxylase activity in liver cells. CYP4A22 loss-of-function reduces the synthesis of 25(OH)D3 and causes genetic compensation of CYP2R1.

UNASSIGNED: We investigate the relationship between the changes of serum 25-hydroxyvitamin D3 (25(OH)D3) and vasohibin-1 (VASH-1) and renal function injury in patients with type 2 diabetic nephropathy.
UNASSIGNED: In this study, 143 patients with diabetic nephropathy (DN) were selected as DN group, and 80 patients with type 2 diabetes mellitus were selected as T2DM group. The serum 25 (OH) D3, VASH-1, blood glucose index, inflammation index and renal function index were compared between the two groups. According to the urinary microalbumin/creatinine ratio (UACR), the DN group was divided into microalbuminuria group (UACR range≥30.0mg/g and <300.0mg/g) and macroalbuminuria group (UACR≥300.0mg/g) for stratified comparison. The correlation between 25-hydroxyvitamin D3, VASH-1 and inflammation index and renal function index was analyzed by simple linear correlation analysis.
UNASSIGNED: The level of 25 (OH) D3 in DN group was significantly lower than that in T2DM group (P<0.05). The levels of VASH-1, CysC, BUN, Scr, 24h urine protein, serum CRP, TGF-β1, TNF-α and IL-6 in DN group were higher than those in T2DM group (P<0.05). The level of 25 (OH) D3 in DN patients with massive proteinuria was significantly lower than that in DN patients with microalbuminuria. The level of VASH-1 in DN patients with massive proteinuria was higher than that in DN patients with microalbuminuria (P<0.05). There was a negative correlation between 25 (OH) D3 and CysC, BUN, Scr, 24h urine protein, CRP, TGF-β1, TNF-α, IL-6 in patients with DN (P<0.05). VASH-1 was positively correlated with Scr, 24h urinary protein, CRP, TGF-β1, TNF-α and IL-6 in patients with DN (P<0.05).
UNASSIGNED: The level of serum 25 (OH) D3 in DN patients was considerably decreased, and the level of VASH-1 was increased, which was related to the degree of renal function injury and inflammatory response.

The study was conducted to evaluate the effects of 25(OH)VD3 with different inclusion levels of 0, 25, 50 and 75 μg/kg in the diet on growth performance, nutrient digestibility, bone properties and pork quality in growing-finishing pigs. The results showed that the average daily gain (p < 0.05) and body weight (p < 0.10) of pigs showed a trend of increasing quadratically as inclusion levels of 25(OH)VD3 increased. Dietary supplementation of 50 μg/kg 25(OH)VD3 increased calcium digestibility compared with the 0 μg/kg group (p < 0.05), and calcium and phosphorus digestibility increased quadratically as inclusion levels of 25(OH)VD3 increased (p < 0.05). Dietary supplementation of 50 μg/kg 25(OH)VD3 increased concentrations of polyunsaturated fatty acids, and decreased contents of saturated and monounsaturated fatty acids in the longissimus dorsi of pigs (p < 0.05). The addition of 25, 50 and 75 μg/kg 25(OH)VD3 to the diet increased breaking strength and bone stiffness in the tibia compared with the 0 μg/kg group (p < 0.05). Dietary supplementation of 50 μg/kg 25(OH)VD3 improved the activities of superoxide dismutase (SOD) and catalase (CAT), and increased the messenger RNA (mRNA) expression of Cu/Zn SOD in the longissimus dorsi compared with the 0 μg/kg group (p < 0.05). Supplementing 50 μg/kg 25(OH)VD3 improved the mRNA expression of calcium-binding protein D9k (CaBP-D9k) and D28k (CaBP-D28K) in the liver compared with the 0 μg/kg 25(OH)D3 group (p < 0.05). In conclusion, a diet with an added dose of 50 μg/kg 25(OH)VD3 showed a greatest growth performance of growing-finishing pigs, and 25(OH)VD3 enhanced calcium deposition and antioxidant capacity in the longissimus dorsi, which may be associated with improved expression of calcium ion channel proteins.

Previous studies suggested that lower vitamin D might be a risk factor for autism spectrum disorders (ASDs). The aim of this study was to estimate the prevalence of ASDs in 3-year-old Chinese children and to examine the association between neonatal vitamin D status and risk of ASDs. We conducted a study of live births who had taken part in expanded newborn screening (NBS), with outpatient follow-up when the children 3-year old. The children were confirmed for ASDs in outpatient by the Autism Diagnostic Interview-Revised and Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria. Intellectual disability (ID) status was defined by the intelligence quotient (IQ < 80) for all the participants. The study design included a 1:4 case to control design. The concentration of 25-hydroxyvitamin D3 [25(OH)D3] in children with ASD and controls were assessed from neonatal dried blood samples. A total of 310 children were diagnosed as having ASDs; thus, the prevalence was 1.11% (95% CI, 0.99% to 1.23%). The concentration of 25(OH)D3 in 310 ASD and 1240 controls were assessed. The median 25(OH)D3 level was significantly lower in children with ASD as compared to controls (p < 0.0001). Compared with the fourth quartiles, the relative risk (RR) of ASDs was significantly increased for neonates in each of the three lower quartiles of the distribution of 25(OH)D3, and increased risk of ASDs by 260% (RR for lowest quartile: 3.6; 95% CI, 1.8 to 7.2; p < 0.001), 150% (RR for second quartile: 2.5; 95% CI, 1.4 to 3.5; p = 0.024), and 90% (RR for third quartile: 1.9; 95% CI, 1.1 to 3.3; p = 0.08), respectively. Furthermore, the nonlinear nature of the ID-risk relationship was more prominent when the data were assessed in deciles. This model predicted the lowest relative risk of ID in the 72rd percentile (corresponding to 48.1 nmol/L of 25(OH)D3). Neonatal vitamin D status was significantly associated with the risk of ASDs and intellectual disability. The nature of those relationships was nonlinear. © 2017 American Society for Bone and Mineral Research.