TY - JOUR T1 - Loss-of-function variants in <em>DNM1</em> cause a specific form of developmental and epileptic encephalopathy only in biallelic state JF - Journal of Medical Genetics JO - J Med Genet SP - 549 LP - 553 DO - 10.1136/jmedgenet-2021-107769 VL - 59 IS - 6 AU - Gökhan Yigit AU - Ruth Sheffer AU - Muhannad Daana AU - Yun Li AU - Emrah Kaygusuz AU - Hagar Mor-Shakad AU - Janine Altmüller AU - Peter Nürnberg AU - Liza Douiev AU - Silke Kaulfuss AU - Peter Burfeind AU - Bernd Wollnik AU - Knut Brockmann Y1 - 2022/06/01 UR - http://jmg.bmj.com/content/59/6/549.abstract N2 - Background Developmental and epileptic encephalopathies (DEEs) represent a group of severe neurological disorders characterised by an onset of refractory seizures during infancy or early childhood accompanied by psychomotor developmental delay or regression. DEEs are genetically heterogeneous with, to date, more than 80 different genetic subtypes including DEE31 caused by heterozygous missense variants in DNM1.Methods We performed a detailed clinical characterisation of two unrelated patients with DEE and used whole-exome sequencing to identify causative variants in these individuals. The identified variants were tested for cosegregation in the respective families.Results We excluded pathogenic variants in known, DEE-associated genes. We identified homozygous nonsense variants, c.97C&gt;T; p.(Gln33*) in family 1 and c.850C&gt;T; p.(Gln284*) in family 2, in the DNM1 gene, indicating that biallelic, loss-of-function pathogenic variants in DNM1 cause DEE.Conclusion Our finding that homozygous, loss-of-function variants in DNM1 cause DEE expands the spectrum of pathogenic variants in DNM1. All parents who were heterozygous carriers of the identified loss-of-function variants were healthy and did not show any clinical symptoms, indicating that the type of mutation in DNM1 determines the pattern of inheritance. ER -