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Late-onset phenotype associated with a homozygous GJC2 missense mutation in a Turkish family.

Authors :
Kuipers, Demy J.S.
Tufekcioglu, Zeynep
Bilgiç, Başar
Olgiati, Simone
Dremmen, Marjolein H.G.
van IJcken, Wilfred F.J.
Breedveld, Guido J.
Mancini, Grazia M.S.
Hanagasi, Haşmet A.
Emre, Murat
Bonifati, Vincenzo
Source :
Parkinsonism & Related Disorders. Sep2019, Vol. 66, p228-231. 4p.
Publication Year :
2019

Abstract

<bold>Objective: </bold>Recessive mutations in the Gap Junction Protein Gamma 2 (GJC2) gene cause Pelizaeus-Merzbacher-like disease type 1, a severe infantile-onset hypomyelinating leukodystrophy. Milder, late-onset phenotypes including complicated spastic paraplegia in one family (SPG44), and mild tremor in one case, were reported associated to GJC2 homozygous missense mutations. Here, we report a new family with two siblings carrying a different homozygous GJC2 mutation, presenting with late-onset ataxic and pyramidal disturbances, and parkinsonism in one of them.<bold>Methods: </bold>Two affected siblings were studied by neurological examination and brain MRI. Genetic analyses included genome-wide homozygosity mapping in both siblings, and whole exome sequencing in one sib. The resulting candidate gene variant was validated by Sanger sequencing.<bold>Results: </bold>The affected siblings share a novel homozygous GJC2 missense mutation (c.820G>C, p.Val274Leu), predicted as pathogenic by all used in-silico tools. Brain MRI showed hyperintense signal in T2-weighted images in the internal capsule and subcortical and periventricular white matter, consistent with hypomyelination.<bold>Conclusions: </bold>Our findings confirm and further expand the late-onset phenotypes of GJC2 mutations, to include prominent ataxia, pyramidal disturbances and mild parkinsonism, and confirm the distinctive associated MRI pattern. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
13538020
Volume :
66
Database :
Academic Search Index
Journal :
Parkinsonism & Related Disorders
Publication Type :
Academic Journal
Accession number :
138916050
Full Text :
https://doi.org/10.1016/j.parkreldis.2019.07.033