Unknown

Dataset Information

0

A common pathomechanism in GMAP-210- and LBR-related diseases.


ABSTRACT: Biallelic loss-of-function mutations in TRIP11, encoding the golgin GMAP-210, cause the lethal human chondrodysplasia achondrogenesis 1A (ACG1A). We now find that a homozygous splice-site mutation of the lamin B receptor (LBR) gene results in the same phenotype. Intrigued by the genetic heterogeneity, we compared GMAP-210- and LBR-deficient primary cells to unravel how particular mutations in LBR cause a phenocopy of ACG1A. We could exclude a regulatory interaction between LBR and GMAP-210 in patients' cells. However, we discovered a common disruption of Golgi apparatus architecture that was accompanied by decreased secretory trafficking in both cases. Deficiency of Golgi-dependent glycan processing indicated a similar downstream effect of the disease-causing mutations upon Golgi function. Unexpectedly, our results thus point to a common pathogenic mechanism in GMAP-210- and LBR-related diseases attributable to defective secretory trafficking at the Golgi apparatus.

SUBMITTER: Wehrle A 

PROVIDER: S-EPMC6328090 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications


Biallelic loss-of-function mutations in TRIP11, encoding the golgin GMAP-210, cause the lethal human chondrodysplasia achondrogenesis 1A (ACG1A). We now find that a homozygous splice-site mutation of the lamin B receptor (LBR) gene results in the same phenotype. Intrigued by the genetic heterogeneity, we compared GMAP-210- and LBR-deficient primary cells to unravel how particular mutations in LBR cause a phenocopy of ACG1A. We could exclude a regulatory interaction between LBR and GMAP-210 in pa  ...[more]

Similar Datasets

| S-EPMC3108191 | biostudies-literature
| S-EPMC4406126 | biostudies-literature
| S-EPMC2148210 | biostudies-literature
| S-EPMC4310744 | biostudies-literature
| S-EPMC1221999 | biostudies-other
| S-BSST407 | biostudies-other
| S-EPMC5425483 | biostudies-literature
| S-EPMC7610725 | biostudies-literature
| S-EPMC7247819 | biostudies-literature
| S-EPMC4695173 | biostudies-literature