biostudies-literatureUnknown10(1)Fichtman BNuclear envelopathies comprise a heterogeneous group of diseases caused by mutations in genes encoding nuclear envelope proteins. Mutations affecting lamina-associated polypeptide 1 (LAP1) result in two discrete phenotypes of muscular dystrophy and progressive dystonia with cerebellar atrophy. We report 7 patients presenting at birth with severe progressive neurological impairment, bilateral cataract, growth retardation and early lethality. All the patients are homozygous for a nonsense mutation in the TOR1AIP1 gene resulting in the loss of both protein isoforms LAP1B and LAP1C. Patient-derived fibroblasts exhibit changes in nuclear envelope morphology and large nuclear-spanning channels containing trapped cytoplasmic organelles. Decreased and inefficient cellular motility is also observedNature communications605https://www.ebi.ac.uk/biostudies/studies/S-EPMC6363790biostudies-literatureCombined loss of LAP1B and LAP1C results in an early onset multisystemic nuclear envelopathy.PMC6363790Spiegel RFichtman BChervinsky EShaag AZagairy FElpeleg OBarsheshet YBen Neriah ZAssa MBiran NHarel AfalseCombined loss of LAP1B and LAP1C results in an early onset multisystemic nuclear envelopathy.Nuclear envelopathies comprise a heterogeneous group of diseases caused by mutations in genes encoding nuclear envelope proteins. Mutations affecting lamina-associated polypeptide 1 (LAP1) result in two discrete phenotypes of muscular dystrophy and progressive dystonia with cerebellar atrophy. We report 7 patients presenting at birth with severe progressive neurological impairment, bilateral cataract, growth retardation and early lethality. All the patients are homozygous for a nonsense mutation in the TOR1AIP1 gene resulting in the loss of both protein isoforms LAP1B and LAP1C. Patient-derived fibroblasts exhibit changes in nuclear envelope morphology and large nuclear-spanning channels containing trapped cytoplasmic organelles. Decreased and inefficient cellular motility is also observed2019-01-01T00:00:00Z2019 Feb2026-04-13T17:21:42.54Z2019-03-26T22:53:24ZS-EPMC63637903072319910.1038/s41467-019-08493-7