GOLGA2, encoding a master regulator of golgi apparatus, is mutated in a patient with a neuromuscular disorder

Abstract

Golgi apparatus (GA) is a membrane-bound organelle that serves a multitude of critical cellular functions including protein secretion and sorting, and cellular polarity. Many Mendelian diseases are caused by mutations in genes encoding various components of GA. GOLGA2 encodes GM130, a necessary component for the assembly of GA as a single complex, and its deficiency has been found to result in severe cellular phenotypes. We describe the first human patient with a homozygous apparently loss of function mutation in GOLGA2. The phenotype is a neuromuscular disorder characterized by developmental delay, seizures, progressive microcephaly, and muscular dystrophy. Knockdown of golga2 in zebrafish resulted in severe skeletal muscle disorganization and microcephaly recapitulating loss of function human phenotype. Our data suggest an important developmental role of GM130 in humans and zebrafish.

Loss of the golgin GM130 causes Golgi disruption, Purkinje neuron loss, and ataxia in mice

“…Further studies will be required to discriminate between these possibilities. Interestingly, a human patient with a loss-of-function GM130 mutation has recently been described (45). This patient lacked any neonatal phenotype, but developed neuromuscular defects in the first year of life.…”

EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality

“…[62][63][64][65] Two of the interactors, GOLGA2 and ZBED1, have been implicated in cell-cycle control and cell proliferation. 66,67 TRIP6 is a positive regulator of lysophosphatidic acid (LPA)-induced cell migration. 68 Finally, three of the proteins whose interactions were perturbed-REL, TRAF2, and TRIP6-play roles in the NF-κB signaling pathway and have been implicated in the processes of hippocampal synaptic plasticity and memory.…”

Loss‐of‐function mutation in RUSC2 causes intellectual disability and secondary microcephaly

“…15 Finally, the possibility of variations in other genes and modifier effects could also be an explanation for the difference in phenotypes seen in our patients. Actually, in addition to its interaction with Rab1b and its possible role in regulating protein trafficking between the endoplasmic reticulum and the Golgi apparatus, there is some preliminary evidence for the direct interaction between iporin and GM130.…”