Functional Evidence of CCDC186 as a New Disease Associated Gene with Endocrine and Central Nervous System Alterations

• DOI: 10.20944/preprints202307.0520.v1
• Publication Date: 2023-07-11T01:09:01Z
• Authors: Luisa Arrabal; Gerard Muñoz-Pujol; Inma Medina; Laura Gort; Judit Garcia-Vill...; Susana Roldan; Frederic Tort; Antonia Ribes
• Keywords: Sanger sequencing

Background: Protein CCDC186 is involved in the maturation of dense core vesicles trans-Golgi network neurons and endocrine cells. To date, only one patient, within a large sequencing study 1000 cases, single case report with variants had previously been described. However, no functional studies any these two cases performed. Methods: Exome from affected individual each family was In addition, Sanger parents siblings also protein assessed cultured fibroblasts or muscle tissue by western blot. Transcriptomic analysis done means RNA sequencing. Results. We identified three patients gypsy families, unrelated to other, same homozygous mutations gene. Clinically, all presented seizures, frontotemporal atrophy, hypomyelination, recurrent infections, disturbances such as severe non ketotic hypoglycemia. Low levels cortisol, insulin growth hormone could be verified patient. All them neonatal onset died between 7 months 4 years age. WES variant gene (c.2215C>T, p.Arg739Ter) index both families. expression demonstrated that practically undetectable tissue. These observations correlated perfectly transcriptomic performed patients, which showed significant reduction mRNA levels. Conclusion. Our provides evidence this have pathogenic effect on reinforces new disease-associated explain combined neurologic alterations detected our