Klammt, J; Neumann, D; Gevers, EF; Andrew, SF; Schwartz, ID; Rockstroh, D; Colombo, R; Sanchez, MA; Vokurkova, D; Kowalczyk, J; Metherell, LA; Rosenfeld, RG; Pfaeffle, R; Dattani, MT; Dauber, A; Hwa, V. Dominant-negative STAT5B mutations cause growth hormone insensitivity with short stature and mild immune dysregulation. Nature Communications. 2018; 9(1).
STAT5B deficiency is a rare autosomal recessive clinical condition associated with growth hormone insensitivity syndrome (GHIS), severe short stature, and immunodeficiency. Here, congenital dominant-negative inactivating STAT5B mutations are identified in patients with postnatal growth failure, eczema and elevated IgE. The dominant-negative effects are demonstrated to be exerted through different pathological mechanisms, manifesting in milder clinical GHIS and general sparing of the immune system.
Varni, JW; Delamater, AM; Hood, KK; Raymond, JK; Chang, NT; Driscoll, KA; Wong, JC; Yi-Frazier, JP; Grishman, EK; Faith, MA; Corathers, SD; Kichler, JC; Miller, JL; Doskey, EM; Heffer, RW; Wilson, DP; Pediatric Quality of Life Inventory 3.2 Diabetes Module Testing Study Consortium. PedsQL 3.2 Diabetes Module for Children, Adolescents, and Young Adults Reliability and Validity in Type 1 Diabetes. Diabetes Care. 2018; 41(10):2064-2071.
There is increasing recognition of the importance of patient reported outcomes (PRO) to accompany clinical measures in diabetes care and research. This study reports on measurement properties of the revised and updated Pediatric Quality of Life Inventory (PedsQL) 3.2 Diabetes Module. Findings support utility of this measure as a PRO for diabetes clinical research, clinical trials, and practice in children, adolescents, and young adults with type 1 diabetes.
Wallace, M; Green, CR; Roberts, LS; Lee, YM; McCarville, JL; Sanchez-Gurmaches, J; Meurs, N; Gengatharan, JM; Hover, JD; Phillips, SA; Ciaraldi, TP; Guertin, DA; Cabrales, P; Ayres, JS; Nomura, DK; Loomba, R; Metallo, CM. Enzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissues. Nature Chemical Biology. 2018; 14(11):1021-1031.
Branched-chain amino acids catabolism is prominently dysregulated in metabolic syndrome and cancer. Using isotope labelled metabolic tracing, this study shows that adipocytes are the main source of de novo monomethyl branched-chain fatty acids (mmBCFAs). mmBCFAs turnover is affected by gender, obesity and hypoxia and could be useful biomarkers for adipose tissue dysregulation.
Heyn, P; Logan, CV; Fluteau, A; Challis, RC; Auchynnikava, T; Martin, C; Marsh, JA; Taglini, F; Kilanowski, F; Parry, DA; Cormier-Daire, V; Fong, C; Gibson, K; Hwa, V; Ibanez, L; Robertson, SP; Sebastiani, G; Rappsilber, J; Allshire, RC; Reijns, MA M; Dauber, A; Sproul, D; Jackson, AP. Gain-of-function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions. Nature Genetics. 2019; 51(1):96-105.
In patients diagnosed with microcephalic dwarfism, de novo gain-of-function missense mutations in DNMT3A (DNA methyltransferase 3 alpha), was shown to result in widespread DNA hypermethylation at Polycomb-regulated regions, genomic regions that contain key developmental genes. These changes in the epigenetic landscape may deplete stem and/or progenitor cell pools, explaining the global growth failure in patients.
Nip, AS Y; Reboussin, BA; Dabelea, D; Bellatorre, A; Mayer-Davis, EJ; Kahkoska, AR; Lawrence, JM; Peterson, CM; Dolan, L; Pihoker, C; SEARCH for Diabetes in Youth Study Group. Disordered Eating Behaviors in Youth and Young Adults With Type 1 or Type 2 Diabetes Receiving Insulin Therapy The SEARCH for Diabetes in Youth Study. Diabetes Care. 2019; 42(5):859-866.
In youth with type 1 diabetes or type 2 diabetes who were treated with insulin, disordered eating behaviors (DEB) were observed in 21.2% of participants with type 1 diabetes and 50.3% of participants with type 2 diabetes. For both types of diabetes, individuals with disordered eating behaviors had a significantly higher BMI z score, lower insulin sensitivity, more depressive symptoms, and poorer quality of life than those without DEB. Diabetic ketoacidosis episodes occurred more frequently in youth with type 1 diabetes with DEB compared to those without DEB.