Sarah Elizabeth Flanagan

Low-level mosaic variants causing the pancreatic disease congenital hyperinsulinism can be detected from blood DNA

This study detects low-level mosaic variants in blood DNA from individuals with congenital hyperinsulinism using tNGS and confirms them with ddPCR.

A 94-bp Deletion in the Promoter of the Beta-Cell Disallowed gene SLC16A1 causing Adult-onset Hyperinsulinism

This study identifies a 94-bp deletion in the SLC16A1 promoter causing hyperinsulinism by increasing MCT1 expression and triggering inappropriate insulin secretion during physical activity.

The minor spliceosome is a master immune regulator

The paper identifies biallelic variants in RNU6ATAC and RNU4ATAC as causes of early-onset autoimmune diabetes and immune dysregulation, showing the minor spliceosome's role in immune regulation.

Chromosome 20p11.2 deletions cause congenital hyperinsulinism via the likely disruption of FOXA2

The paper identifies chromosome 20p11.2 deletions as a cause of congenital hyperinsulinism by disrupting FOXA2 expression in pancreatic beta-cells.

Rare disease gene association discovery from burden analysis of the 100,000 Genomes Project data

The paper identifies 88 novel rare disease-gene associations using a burden analysis framework on whole genome sequencing data from the 100,000 Genomes Project, with potential clinical impact for undiagnosed cases.

REVEL is better at predicting pathogenicity of loss-of-function than gain-of-function variants

The paper evaluates REVEL's performance in predicting pathogenicity of loss-of-function and gain-of-function variants, finding it better at predicting pathogenicity for loss-of-function variants.

Primate-specific ZNF808 is essential for pancreatic development in humans

The paper identifies homozygous loss of function variants in ZNF808 as a cause of pancreatic agenesis in humans, showing its role in repressing transposable elements during pancreatic development.

A homozygous p.(Arg371Ser) mutation in FICD de-regulates AMPylation of the human endoplasmic reticulum chaperone BiP causing infancy-onset diabetes and severe neurodevelopmental delay

A novel disease mechanism leading to the expression of a disallowed gene in the pancreatic beta-cell identified by non-coding, regulatory mutations controlling HK1

The paper identifies non-coding mutations in a regulatory element of HK1 that lead to inappropriate expression in pancreatic beta-cells and cause congenital hyperinsulinism.

SavvyCNV: genome-wide CNV calling from off-target reads

SavvyCNV calls genome-wide CNVs using off-target reads from exome and targeted sequencing, outperforming existing tools and detecting clinically relevant CNVs previously missed.

Sex-biased islet β cell dysfunction is caused by the MODY MAFA S64F variant by inducing premature aging and senescence in males

This paper identifies a MAFA S64F variant causing sex-dependent β cell dysfunction and diabetes by accelerating aging and senescence in males.

Neonatal diabetes mutations disrupt a chromatin pioneering function that activates the human insulin gene

The paper shows that a mutation associated with neonatal diabetes disrupts chromatin activation of the insulin gene in human cells.

Comprehensive screening shows that mutations in the known syndromic genes are rare in individuals presenting with hyperinsulinaemic hypoglycaemia

The paper screens for syndromic gene mutations in individuals with hyperinsulinaemic hypoglycaemia (HH) and finds a rare pathogenic variant in KMT2D associated with Kabuki syndrome.

Heterozygous RFX6 protein truncating variants cause Maturity-Onset Diabetes of the Young (MODY) with reduced penetrance

This study identifies heterozygous RFX6 protein truncating variants as a cause of MODY with reduced penetrance, using genetic analysis and cohort comparisons.