p.Gly2019Ser: the common LRRK2 mutation

DNA breakage, LRRK2 p.Gly2019SerLRRK2 p.Gly2019Ser

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of inherited Parkinson’s disease (PD), and also a risk factor for idiopathic PD. The LRRK2 missense mutation p.Gly2019Ser, which causes the substitution of a glycine with a serine at codon 2019 of the amino acidic chain, is the most common LRRK2 mutation. The penetrance of this mutation is incomplete and is age-dependent. Therefore, it has been speculated that environmental toxins and aging could contribute to the pathogenesis of the disorder associated to this mutation.

The above mutation leads to increased kinase activity. Based on this evidence concerted efforts have been carried out to identify LRRK2 kinase inhibitors as a potential disease-modifying therapy for PD .

The p.Gly2019Ser mutation of LRRK2 may contribute to the development of PD by inhibiting microglial response to brain injury. Substantia nigra hyperechogenicity, which has been proposed as a risk marker of Parkinson’s disease, is frequent in both symptomatic and asymptomatic LRRK2 p.Gly2019Ser carriers.

References: OMIM: 609007, 607060.

Posted in Academia, Free Mutation, Last Update, Medical Genetics, Mutations and tagged , , .

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