Alfredo Brusco

Functional validation of allele-specific LMNB1 silencing in patient-derived astrocytes as a therapeutic option for Autosomal Dominant Leukodystrophy

This study validates allele-specific LMNB1 silencing in patient-derived astrocytes as a therapeutic approach for ADLD by showing restored physiological levels and functional improvements.

Rare variation illuminates the distinct and pleiotropic genetic architecture of autism across neuropsychiatric traits

The paper identifies 253 autism-associated genes using rare variation from 62,429 individuals and finds pleiotropy across physiological systems and developmental disorders.

Genetic variants in DDX53 contribute to Autism Spectrum Disorder associated with the Xp22.11 locus

The paper identifies DDX53 genetic variants in individuals with ASD, showing a link between DDX53 and ASD, and highlights implications for genetic testing and mouse modeling.

Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles

The paper identifies variant-specific effects of AFF3 on transcriptome profiles through analysis of patient cohorts and zebrafish models, showing distinct pathophysiological mechanisms for different types of AFF3 variants.

The crucial role of titin in fetal development: recurrent miscarriages and bone, heart, and muscle anomalies characterize the severe end of titinopathies spectrum

This study identifies severe developmental anomalies and high miscarriage rates in patients with biallelic titin truncating variants, highlighting the need for TTN evaluation in congenital musculoskeletal and cardiac conditions.

Deleterious, protein-altering variants in the X-linked transcriptional coregulator ZMYM3 in 22 individuals with a neurodevelopmental delay phenotype

The paper identifies ZMYM3 variants in 22 individuals with neurodevelopmental delay, showing recurrent mutations, phenotypic overlap, and functional effects, supporting ZMYM3 as a novel NDD gene.

SETBP1 variants outside the degron disrupt DNA-binding and transcription independent of protein abundance to cause a heterogeneous neurodevelopmental disorder

The paper investigates SETBP1 variants outside the degron, showing they cause a heterogeneous neurodevelopmental disorder through loss-of-function mechanisms independent of protein abundance.

Drosophila functional screening of de novo variants in autism uncovers deleterious variants and facilitates discovery of rare neurodevelopmental diseases

The paper functionally tests ASD missense variants in Drosophila, finding 38% caused functional alterations and identifying GLRA2 as a cause of neurodevelopmental phenotypes.

CCG*CGG interruptions in high penetrance SCA8 families increase RAN translation and protein toxicity

This study shows that CCG*CGG interruptions in SCA8 repeat expansions increase RAN protein levels and toxicity, contributing to higher disease penetrance.

ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population

The paper identifies ACE2 gene variants associated with interindividual variability in COVID-19 susceptibility in the Italian population using whole-exome-sequencing data.

Variants in the degron of AFF3 cause a multi-system disorder with mesomelic dysplasia, horseshoe kidney and developmental and epileptic encephalopathy

The paper identifies degron variants in AFF3 causing a multi-system disorder with specific clinical features and demonstrates phenotypic overlap with AFF4-related syndromes.

Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism

This study identifies 99 genes associated with autism spectrum disorder through large-scale exome sequencing, showing differences in mutation frequencies between ASD and severe neurodevelopmental delay groups.

Mice harboring a SCA28 patient mutation in AFG3L2 develop late-onset ataxia associated with enhanced mitochondrial proteotoxicity.

This study creates a new mouse model with a patient-derived SCA28 mutation and shows it leads to late-onset ataxia and mitochondrial dysfunction.