RDMM-Europe – Solve-RD

RDMM-Europe project published!

Solve-RD partners and Henry Houlden at the UCL Queen Square Institute of Neurology identified novel missense variants in the gene ACBD6 in a large cohort of unrelated patients with complex dystonia parkinsonism ataxia phenotype. The patients presented moderate-to-severe delay in psychomotor development predominantly affecting the acquisition of walking skills, speech, intellectual functioning (global developmental delay, moderate to severe intellectual disability, severe speech disorder, diverse behavioural abnormalities), variable dysmorphisms and seizures. The RDMM-Europe committees suggested to connect the group with Gaurav K. Varshney at the Oklahoma Medical Research Foundation and Solve-RD provided Seeding Grant funding to support the validation of the gen disease association using zebrafish as a model.

The collaborative work was now accepted for publication in Brain.

Rauan Kaiyrzhanov, Aboulfazl Rad, Sheng-Jia Lin [...] Reza Maroofian. Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders. Brain (2023) https://doi.org/10.1093/brain/awad380

RDMM-Europe project published!

Stefan Barakat and Tjakko van Ham at Erasmus University Medical Center in Rotterdam have received a Seeding Grant via the Solve-RD Rare Disease Models & Mechanisms Network (RDMM-Europe) program in May 2022. The funding supported their work to confirm pathogenicity of AMFR dysfunction causing autosomal recessive spastic paraplegia (HSP) by using zebrafish models. AMFR was proposed for functional validation within the RDMM programme by Solve-RD partners Reza Maroofian and Henry Houlden at the UCL Queen Square Institute of Neurology. They have initially identified a homozygous frameshift mutation of AMFR within a shared RoH region in two affected siblings suffering from Hereditary Spastic Paraplegia (HSP). By international collaborations and data sharing similar biallelic loss of function mutations of the same gene were found in a total of 20 affected individuals from 8 consanguineous families.

The collaborative work was now accepted for publication in Acta Neuropathologica.

Ruizhi Deng, Eva Medico-Salsench, Anita Nikoncuk et al. AMFR dysfunction causes autosomal recessive spastic paraplegia in human that is amenable to statin treatment in a preclinical model. Acta Neuropathol (2023). https://doi.org/10.1007/s00401-023-02579-9

RDMM-Europe project published!

Solve-RD partners Antonio Vitobello from the University Hospital Dijon-Bourgogne and Elke Bogaert & Bart Dermaut from Ghent University in Belgium were connected by our European Rare Disease Models & Mechanisms Network (RDMM-Europe) initiative. They received Seeding Grant funding to generate Drosophila models that support the validation of new SRSF1 variants identified in a cohort of patients with syndromic developmental disorder associated with intellectual disability. Their findings have now been accepted for publication in The American Journal of Human Genetics.

Elke Bogaert, Aurore Garde, Thierry Gautier et al. SRSF1 haploinsufficiency is responsible for a syndromic developmental disorder associated with intellectual disability. The American Journal of Human Genetics (2023). https://doi.org/10.1016/j.ajhg.2023.03.016