Body proportions in patients with Turner syndrome on growth hormone treatment.

BACKGROUND: : In this cross-sectional study, we aimed to evaluate auxological measurements and detailed body proportions of recombinant human growth hormone (GH)-treated patients with Turner syndrome (TS) and compare them with a group of healthy females. METHODS: We evaluated 42 patients with TS who received GH treatment and 20 healthy controls. Anthropometric measurements were taken and target height, body mass index (BMI), arm span-height difference, extremity-to-trunk ratio, and Manouvrier's skelic index were calculated. RESULTS: : The median (min-max) age of the patients at the time of evaluation was 13.6 (4.3-20.7) years, and the control group was 12.9 (3.8-23.7) years. Height, sitting height, and arm span of TS patients were significantly lower than those of the control group. Sitting height/height ratio (SHR) was in normal ranges in both groups and BMI was significantly higher in TS patients when compared to the control group. According to Manouvrier's skelic index, TS patients had shorter legs than the control group (p = 0.001). The extremity-trunk ratio was significantly decreased in TS patients compared to healthy controls (p < 0.001). There was no significant difference between the karyotype groups in terms of these indexes. DISCUSSION: TS patients had short stature, increased BMI and waist circumference, normal head circumference, and decreased extremity-trunk ratio. Sitting height and leg length were short; however, the SHR standard deviation score (SDS) was in the normal range. Despite being treated with GH, TS patients had disproportionate short stature. The disproportion in TS patients was similar to short-stature homeobox-containing gene (SHOX) deficiency, which is considered to be SHOX haploinsufficiency in the etiopathogenesis of short stature.

Monogenic Childhood Diabetes: Dissecting Clinical Heterogeneity by Next-Generation Sequencing in Maturity-Onset Diabetes of the Young.

Diabetes is a common disorder with a heterogeneous clinical presentation and an enormous burden on health care worldwide. About 1-6% of patients with diabetes suffer from maturity-onset diabetes of the young (MODY), the most common form of monogenic diabetes with autosomal dominant inheritance. MODY is genetically and clinically heterogeneous and caused by genetic variations in pancreatic ß-cell development and insulin secretion. We report here new findings from targeted next-generation sequencing (NGS) of 13 MODY-related genes. A sample of 22 unrelated pediatric patients with MODY and 13 unrelated healthy controls were recruited from a Turkish population. Targeted NGS was performed with Miseq 4000 (Illumina) to identify genetic variations in 13 MODY-related genes: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8, and KCNJ11. The NGS data were analyzed adhering to the Genome Analysis ToolKit (GATK) best practices pipeline, and variant filtering and annotation were performed. In the patient sample, we identified 43 MODY-specific genetic variations that were not present in the control group, including 11 missense mutations and 4 synonymous mutations. Importantly, and to the best of our knowledge, the missense mutations NEUROD1 p.D202E, KFL11 p.R461Q, BLK p.G248R, and KCNJ11 p.S385F were first associated with MODY in the present study. These findings contribute to the worldwide knowledge base on MODY and molecular correlates of clinical heterogeneity in monogenic childhood diabetes. Further comparative population genetics and functional genomics studies are called for, with an eye to discovery of novel diagnostics and personalized medicine in MODY. Because MODY is often misdiagnosed as type 1 or type 2 diabetes mellitus, advances in MODY diagnostics with NGS stand to benefit diabetes overall clinical care as well.