In the largest cohort to date, we demonstrate a wide spectrum of phenotypes and biological profiles in patients with 5α-reductase deficiency, whatever their geographical or ethnic origins.

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The identification of a second case of severe growth failure associated with STAT5b mutation implicates a unique and critical role for STAT5b in GH stimulation of IGF-I gene expression and statural growth.

Next-generation sequencing (NGS) enables analysis of the human genome on a scale previously unachievable by Sanger sequencing. Exome sequencing of the coding regions and conserved splice sites has been very successful in the identification of disease-causing mutations, and targeting of these regions has extended clinical diagnostic testing from analysis of fewer than ten genes per phenotype to more than 100. Noncoding mutations have been less extensively studied despite evidence from mRNA analysis for the existence of deep intronic mutations in >20 genes. We investigated individuals with hyperinsulinaemic hypoglycaemia and biochemical or genetic evidence to suggest noncoding mutations by using NGS to analyze the entire genomic regions of ABCC8 (117 kb) and HADH (94 kb) from overlapping ~10 kb PCR amplicons. Two deep intronic mutations, c.1333-1013A>G in ABCC8 and c.636+471G>T HADH, were identified. Both are predicted to create a cryptic splice donor site and an out-of-frame pseudoexon. Sequence analysis of mRNA from affected individuals' fibroblasts or lymphoblastoid cells confirmed mutant transcripts with pseudoexon inclusion and premature termination codons. Testing of additional individuals showed that these are founder mutations in the Irish and Turkish populations, accounting for 14% of focal hyperinsulinism cases and 32% of subjects with HADH mutations in our cohort. The identification of deep intronic mutations has previously focused on the detection of aberrant mRNA transcripts in a subset of disorders for which RNA is readily obtained from the target tissue or ectopically expressed at sufficient levels. Our approach of using NGS to analyze the entire genomic DNA sequence is applicable to any disease.

Objective: Materno-fetal vitamin D deficiency (VDD) may occur in the early neonatal period. We aimed to evaluate the vitamin D (vitD) status and risk factors for VDD in healthy newborns and their mothers, and also in fertile women. Methods: Serum 25 hydroxyvitamin D3 (25(OH)D), calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) levels were measured in 70 mothers (study group) and their newborns, and in umbilical cord samples. 104 nonpregnant fertile women comprised the control group. Demographic factors such as education and clothing habits of the mother, number of pregnancies and month of delivery were recorded. A serum 25(OH)D level below 11 ng/ml was accepted as severe, 11-25 ng/ml as moderate VDD, and a value over 25ng/ml as normal. Results: Severe VDD was found in 27% of the mothers, and moderate deficiency in 54.3%. Severe VDD was detected in 64.3% of the neonates, and moderate deficiency in 32.9%. Only 18.6% of the mothers and 2.9 % of the neonates had normal vitD levels. In thecontrol group, severe VDD was observed in 26.9%, and moderatedeficiency in 45.2 %. Only 27.8 % of the controls had normal vitD levels. In the control group, the 25(OH)D levels of the women dressed in modern clothes were significantly higher than those of the women wearing traditional clothes. This difference was not observed in the study group because 75% of these 70 mothers wore modern clothes. Mothers giving birth during the summer months and their neonates had significantly higher serum 25(OH)D levels than those of the mothers giving birth during the winter months and their neonates. Conclusion: The study has shown that in Turkey VDD is an important problem in women of reproductive age, in mothers and their neonates. The 25(OH)D levels obtained from the cord may serve as a guide in the determination of the high risk groups.Conflict of interest:None declared.