Role of chromosomal imbalances in the pathogenesis of DSD: A retrospective analysis of 115 prenatal samples.

Differences of sex development (DSDs) are a group of congenital conditions characterized by a discrepancy between chromosomal, gonadal, and genital sex development of an individual, with significant impact on medical, psychological and reproductive life. The genetic heterogeneity of DSDs complicates the diagnosis and almost half of the patients remains undiagnosed. In this context, chromosomal imbalances in syndromic DSD patients may help to identify new genes implicated in DSDs. In this study, we aimed at describing the burden of chromosomal imbalances including submicroscopic ones (copy number variants or CNVs) in a cohort of prenatal syndromic DSD patients, and review their role in DSDs. Our patients carried at least one pathogenic or likely pathogenic chromosomal imbalance/CNV or low-level mosaicism for aneuploidy. Almost half of the cases resulted from an unbalanced chromosomal rearrangement. Chromosome 9p/q, 4p/q, 3q and 11q anomalies were more frequently observed. Review of the literature confirmed the causative role of CNVs in DSDs, either in disruption of known DSD-causing genes (SOX9, NR0B1, NR5A1, AR, ATRX, …) or as a tool to suspect new genes in DSDs (HOXD cluster, ADCY2, EMX2, CAMK1D, …). Recurrent CNVs of regulatory elements without coding sequence content (i.e. duplications/deletions upstream of SOX3 or SOX9) confirm detection of CNVs as a mean to explore our non-coding genome. Thus, CNV detection remains a powerful tool to explore undiagnosed DSDs, either through routine techniques or through emerging technologies such as long-read whole genome sequencing or optical genome mapping.

Impact of OMNIPOD® on the quality of life of adolescents with type 1 diabetes.

INTRODUCTION: Several pediatric studies have demonstrated that therapy using a conventional insulin pump improves glycemic control and quality of life. At the beginning of this study, a new tubeless insulin pump, Omnipod®, had recently been marketed in France. OBJECTIVES: Analyze the response of adolescents treated with multiple injections to the proposal to use this new medical device and compare both the quality of life and the glycemic control of adolescents according to their choice. MATERIAL AND METHODS: This was a prospective, observational study of adolescents aged 10-17 years who had type 1 diabetes for more than 1 year, all treated with multi-injection insulin delivery according to a basal-bolus regimen. They were separated into three groups: group A choosing to use the Omnipod® system, group B taking the time to think before making a decision, and group C choosing to keep their multi-injection therapy. The three groups were compared according to their quality of life with validated tools and glycemic control. RESULTS: Groups were formed with 30 (25%) patients in group A, 55 patients (45%) in group B, and 36 patients (30%) in group C. As to the WHO Well-Being Index, no significant difference appeared in the study for the patients in the three groups. An increased treatment satisfaction score was found, evolving from 3.79 ± 0.68 to 4.36 ± 0.56, p = 0.002 (group A) and from 3.87 ± 0.7 to 4.16 ± 0.7, p = 0.032 (group B), with no significant change for group C (from 4.39 ± 0.6 to 4.31 ± 0.62, p = 0.582). The wish to change treatment score improved for group A (from 4.14 ± 0.88 to 1.68 ± 0.9; p < 0.001) and group B (from 3.51 ± 1.05 to 1.84 ± 1; p < 0.001), with no significant change for group C (from 1.81 ± 0 0.98 to 1.61 ± 0.8; p = 0.432). There was no significant difference regarding HbA1c rates in the three groups. CONCLUSION: There was no significant difference in quality-of-life scores between adolescents who chose to switch from multiple injection to the tubeless patch pump and those who retained multi-injection treatment, but increased satisfaction was observed in the former group.