Combined loss of LAP1B and LAP1C results in an early onset multisystemic nuclear envelopathy

Boris Fichtman, Fadia Zagairy, Nitzan Biran, Yiftah Barsheshet, Elena Chervinsky, Ziva Neriah, Avraham Shaag, Michael Assa, Orly Elpeleg, Amnon Harel () and Ronen Spiegel ()
Additional contact information
Boris Fichtman: Bar-Ilan University
Fadia Zagairy: Bar-Ilan University
Nitzan Biran: Bar-Ilan University
Yiftah Barsheshet: Bar-Ilan University
Elena Chervinsky: Genetic Institute, Emek Medical Center
Ziva Neriah: Shaare Zedek Medical Center
Avraham Shaag: Hadassah-Hebrew University Medical Center
Michael Assa: Bar-Ilan University
Orly Elpeleg: Hadassah-Hebrew University Medical Center
Amnon Harel: Bar-Ilan University
Ronen Spiegel: Emek Medical Center

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract 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 observed in these fibroblasts. Our study describes the complete absence of both major human LAP1 isoforms, underscoring their crucial role in early development and organogenesis. LAP1-associated defects may thus comprise a broad clinical spectrum depending on the availability of both isoforms in the nuclear envelope throughout life.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-08493-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08493-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-08493-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().