Structural Variants at the LMNB1 Locus: Deciphering Pathomechanisms in Autosomal Dominant Adult-Onset Demyelinating Leukodystrophy.
Paola DimartinoMariia ZadorozhnaVerónica YumicebaAnna BasileIlaria CaniUirá Souto MeloJana HenckMarjolein BreurCaterina TononRaffaele LodiAlfredo BruscoTommaso PippucciFoteini-Dionysia KoufiElisa BoschettiGiulia RamazzottiLucia ManzoliStefano RattiFilippo Pinto E VairoMartin B DelatyckiGiovanna VaulaPietro CortelliMarianna BugianiMalte SpielmannElisa GiorgioPublished in: Annals of neurology (2024)
Our study sheds light on the 3D genome and TAD structural changes associated with SVs in the LMNB1 locus, and shows that a duplication encompassing LMNB1 is not sufficient per se to diagnose ADLD, thereby strongly affecting genetic counseling. Our study supports breaking TADs as an emerging pathogenic mechanism that should be considered when studying brain diseases. ANN NEUROL 2024.