A Phase 2, Six-Month Safety and Efficacy Study of TransCon hGH Compared to Daily hGH in Pre-Pubertal Children with Growth Hormone Deficiency (GHD)

This study demonstrates the safety and efficacy of TransCon hGH in children with GHD over a treatment period of six months. Safety and efficacy (annualized height velocity), as well as PK and PD data of 53 GHD patients treated over a six-month period with TransCon hGH or daily hGH will be presented. All TransCon hGH doses demonstrated an excellent safety (comparable to daily hGH) and local tolerability profile (only mild and sporadic reactions comparable to daily hGH / no nodule formation and lypodystrophy) and an excellent growth within the expected ranges - mean annualized height velocities ranging between 11.9 cm to 13.9 cm for the different dose levels of TransCon hGH compared to 11.6 cm mean annualized height velocity for daily hGH treatment

High frequency of mutations in 'dyshormonogenesis genes' in severe congenital hypothyroidism.

OBJECTIVE:Results of the screening of disease causative mutations in congenital hypothyroidism (CH) vary significantly, depending on the sequence strategy, patients' inclusion criteria and bioinformatics. The objective was to study the molecular basis of severe congenital hypothyroidism, using the next generation sequencing (NGS) and the recent guidelines for assessment of sequence variants. DESIGN:243 patients with CH (TSH levels at neonatal screening or retesting greater than 90 mU/l) and 56 control subjects were included in the study. METHODS:A custom NGS panel targeting 12 CH causative genes was used for sequencing. The sequence variants were rated according to American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS:In total, 48 pathogenic, 7 likely pathogenic and 57 variants of uncertain significance were identified in 92/243 patients (37.9%), while 4 variants of uncertain significance were found in 4/56 control subjects (7.1%). 13.1% (12/92) of the cases showed variants in 'thyroid dysgenesis' (TD) genes: TSHR, n = 6; NKX2-1, n = 2; NKX2-5, n = 1; PAX8, n = 3. The variants in 'dyshormonogenesis' (DH) genes were found in 84.8% (78/92) of cases: TPO, n = 30; DUOX2, n = 24; TG, n = 8; SLC5A5, n = 3; SLC26A4, n = 6; IYD, n = 1. 8 patients showed oligonenic variants. The majority of variants identified in DH genes were monoallelic. CONCLUSIONS:In contrast to earlier studies demonstrating the predominance of TD in severe CH, the majority of variants identified in our study were in DH genes. A large proportion of monoallelic variants detected among DH genes suggests that non-mendelian mechanisms may play a role in the development of CH