Good parent well-being is associated with bitter metabolic control, less family burden and better quality of life in 2062 adolescents with Type 1 Diabetes

Good parent well-being is associated with bitter metabolic control, less family burden and better quality of life in 2062 adolescents with Type 1 Diabete

Additional file 1: of Diabetes MILES Youth–Australia: methods and sample characteristics of a national survey of the psychological aspects of living with type 1 diabetes in Australian youth and their parents

Description of scales used in the Diabetes MILES Youth Study. (PDF 201 kb

Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort

Background: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. Results: We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46,XY DSD and 48 with 46,XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46,XY DSD. In patients with 46,XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management. Conclusions: Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes

SARS-CoV-2 Infection and Childhood Islet Autoimmunity

This cohort study examines whether there is a temporal association between SARS-CoV-2 infection and the development of islet autoimmunity among Australian children with a first-degree relative with type 1 diabetes

Additional file 1: Table S1. of Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort

DSD gene variants. Each variant found in a diagnostic gene (after the filtering and curation process) is shown. In some cases where the gene is inherited in an autosomal recessive manner, two variants are grouped together. Inheritance has been indicated where familial samples were available: negative indicates negative for variant and N/A sample not available. De novo events have only been noted where both parental samples were available and found to be negative for the change. Previously reported refers to a variant being described in either ClinVar, HGMD, or a publication in a peer-reviewed journal via a PubMed search. Variants were classified consistent with previous MPS publications of DSD cohorts [8, 10] which were based on ACMG guidelines [15]. VUS were called for three reasons: 1 = fits phenotype but predicted to be benign; 2 = damaging but doesn’t fit phenotype; or 3 = variant in the AR repetitive region. Patients marked with an asterisk were identified to have two or more diagnostic gene variants. Null variants (frameshifts, splice sites mutations, and premature stop codons) are shown in bold. Patients have been classified based on clinical notes provided, according to the recommended classification of DSD in the Chicago consensus report. Classifications: CGD complete gonadal dysgenesis, DASA disorders of androgen synthesis or action, DSD DSD of “unknown” origin; hypospadias, LCH Leydig cell hypoplasia, OT ovotesticular DSD, PGD partial gonadal dysgenesis, PMDS persistent Müllerian duct syndrome; syndromic, T testicular DSD. Related affected individuals are indicated. File is in Excel spreadsheet format. (XLSX 47 kb