Biallelic frameshift variants in PHLDB1 cause mild-type osteogenesis imperfecta with regressive spondylometaphyseal changes.

BACKGROUND: Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders characterised by susceptibility to fractures, primarily due to defects in type 1 collagen. The aim of this study is to present a novel OI phenotype and its causative candidate gene. METHODS: Whole-exome sequencing and clinical evaluation were performed in five patients from two unrelated families. PHLDB1 mRNA expression in blood and fibroblasts was investigated by real-time PCR, and western blot analysis was further performed on skin fibroblasts. RESULTS: The common findings among the five affected children were recurrent fractures and/or osteopaenia, platyspondyly, short and bowed long bones, and widened metaphyses. Metaphyseal and vertebral changes regressed after early childhood, and no fractures occurred under bisphosphonate treatment. We identified biallelic NM_001144758.3:c.2392dup and NM_001144758.3:c.2690_2693del pathogenic variants in PHLDB1 in the affected patients, respectively, in the families; parents were heterozygous for these variants. PHLDB1 encodes pleckstrin homology-like domain family B member-1 (PHLDB1) protein, which has a role in insulin-dependent Akt phosphorylation. Compared with controls, a decrease in the expression levels of PHLDB1 in the blood and skin fibroblast samples was detected. Western blot analysis of cultured fibroblasts further confirmed the loss of PHLDB1. CONCLUSION: Two biallelic frameshift variants in the candidate gene PHLDB1 were identified in independent families with a novel, mild-type, autosomal recessive OI. The demonstration of decreased PHLDB1 mRNA expression levels in blood and fibroblast samples supports the hypothesis that PHLDB1 pathogenic variants are causative for the observed phenotype.

Effects of injectable trace element and vitamin supplementation during the gestational, peri-parturient, or early lactational periods on neutrophil functions and pregnancy rate in dairy cows.

The aim of this study was to evaluate effects of injectable trace element and vitamin combination on phagocytic, oxidative burst activity of neutrophils and reproductive outcomes in dairy cows. Cows were to assigned to the following groups: (1) injectable trace element supplementation (ITES, n = 44, containing zinc, manganese, copper, selenium); (2) injectable vitamin supplementation (VIT, n = 48, containing vitamins A, D3, E); (3) ITES + VIT (n = 46); and (4) control (CON, n = 44). Cows were administered four injections between 230 and 260 days of the gestational period, on day of parturition, and 30 days postpartum. Neutrophil function was assessed at 10 days before and after calving. Phagocytosis was greater in cows of the ITES + VIT group at 10 days prepartum (P < 0.05) while oxidative burst was similar among groups. There were greater non-esterified fatty acid (NEFA) concentrations in cows of the ITES+VIT group at 10 days prepartum (P < 0.05). Cows supplemented with ITES+ VIT had less SOD activity than those supplemented with ITES or vitamin during the pre- to post-partum transition period (P < 0.05). The total odds of pregnancy were greater in cows supplemented with trace element and/or vitamin (P < 0.05). In conclusion, supplementation of ITES and/or VIT resulted in an increased total pregnancy rate. Vitamin or trace element supplementation did not differ with the control group in both the prepartum and postpartum period for immune variables. There, however, was greater phagocytosis in cows supplemented with vitamin and trace elements during the prepartum period that might be related to metabolic-induced inflammation.

Iodine status of Turkish pregnant women and their offspring: A national cross-sectional survey.

BACKGROUND: This national cross-sectional survey aimed to assess the iodine status in pregnant women and their offspring, and also to demonstrate regional differences by measuring urinary iodine concentration (UIC). For each woman and her newborn a questionnaire was prepared with basic facts as age, parity number or birth weight and additional information regarding thyroid diseases, use of iodized salt in the household, extra iodine supplementation during pregnancy, education level and wage income. METHODS: The target population represented 1444 pregnant women who gave birth between January 1 st, 2018 and 2019, and their offspring. Iodine deficiency for pregnant women and their offspring were defined as urine iodine level <150 µg/L and <100 µg/L, respectively. Results are given as median (25th-75th percentile). RESULTS: The median UIC in the group of pregnant woman was 94 (52-153) µg/L. Within the sample of 1444 pregnant women, UIC indicative of mild iodine deficiency (100-149 µg/L) was present in 21 % (n = 306), moderate deficiency (50-99 µg/L) in 30 % (n = 430), and severe deficiency (<50 µg/L) in 23 % (n = 337). This study showed a prevalence of 74 % of iodine deficiency in Turkish pregnant woman. The median UIC in the group of offspring was 96 (41-191) µg/L. Within the new-borns, UIC indicative of mild iodine deficiency (50-99 µg/L) was present in 22 % (n = 323), moderate deficiency (20-49 µg/L) in 15 % (n = 222), and severe deficiency (<20 µg/L) in 13 % (n = 192). This survey showed a prevalence of 51 % of iodine deficiency in Turkish new-borns. Pregnant women with lower socioeconomic and education level, lower access to household iodized salt, lower rates of exposure to povidone-iodine containing skin disinfectant, higher parity and higher iodine deficiency had higher rates of iodine deficiency in their offspring. Regional differences were observed both in mothers and their offspring concerning their iodine status. CONCLUSIONS: Our findings suggest that iodine deficiency is still an important public health problem in Turkey. More drastic measures should be taken to decrease these important iodine deficiencies, both in pregnant women and in their offspring.