Alexander P.A. Stegmann

Clinical long-read genome sequencing for rare disease diagnostics

This study evaluates long-read genome sequencing in rare disease diagnostics, finding high concordance with standard-of-care tests and incremental diagnostic benefits.

Genotype-Phenotype Correlation in RBM10-Associated Syndromes. How Variant Function Shapes a Broad Phenotypic Landscape

The paper reports 37 new cases of RBM10 variants, identifies two phenotypic groups, and establishes a genotype-phenotype correlation based on functional studies.

Genome sequencing as a generic diagnostic strategy for rare disease

This study evaluates genome sequencing as a primary diagnostic tool for rare diseases, finding it can detect 95% of clinically relevant variants with a 0.3% false negative rate.

Loss-of-function variants in CUL3 cause a syndromic neurodevelopmental disorder

The paper reports a cohort of 35 individuals with CUL3 variants causing a syndromic neurodevelopmental disorder, showing loss-of-function variants disrupt protein homeostasis by impairing proteasomal degradation of CUL3 substrates.

Systematic analysis and prediction of genes associated with disorders on chromosome X

The paper systematically analyzes chrX genes to predict disease associations, identifying 235 genes likely involved in disorders and reporting damaging variants in CDK16 and TRPC5 in patients with intellectual disability or autism.

Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded protein

This study identifies ANKRD11 missense variants as a cause of KBG syndrome by impairing protein stability or transcriptional activity, supporting haploinsufficiency as the underlying mechanism.

Genotype-phenotype correlations and novel molecular insights into the DHX30-associated neurodevelopmental disorders

This study identifies 25 individuals with DHX30 mutations, showing two clinical subtypes based on variant type and severity of developmental and neurological symptoms.

Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction

The paper identifies mutation-specific pathophysiological mechanisms in SATB1 variants causing distinct neurodevelopmental disorders.

Functional analysis of a hypomorphic allele shows that MMP14 catalytic activity is the prime determinant of the Winchester syndrome phenotype

The paper identifies a hypomorphic MMP14 mutation in Winchester syndrome and shows its catalytic activity determines disease severity using in vitro and zebrafish models.

Meta-analysis of 2,104 trios provides support for 10 novel candidate genes for intellectual disability

This study identifies 10 novel candidate genes for intellectual disability through a meta-analysis of de novo mutations from 2,104 trios.