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Eur J Med Genet. 2019 Nov 26:103821. doi: 10.1016/j.ejmg.2019.103821. [Epub ahead of print]

Whole exome sequencing identifies a homozygous POLG2 missense variant in an adult patient presenting with optic atrophy, movement disorders, premature ovarian failure and mitochondrial DNA depletion.

Author information

1
Dept. of Neurology, P.J. Safarik University, Kosice, Slovakia; Dept. of Neurology, University Hospital L. Pasteur, Kosice, Slovakia. Electronic address: petradosekova@gmail.com.
2
Intercollegiate Faculty of Biotechnology of the University of Gdansk and Medical University of Gdansk, Gdansk, Poland.
3
Dept. of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
4
Dept. of Medical Biology, P. J. Safarik University, Kosice, Slovakia.
5
Dept. of Medical Genetics, Medical University of Warsaw, Warsaw, Poland; Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland.
6
Dept. of Ophtalmology, P. J. Safarik University and University Hospital L. Pasteur, Kosice, Slovakia.
7
Dept. of Neurology, P.J. Safarik University, Kosice, Slovakia; Dept. of Neurology, University Hospital L. Pasteur, Kosice, Slovakia.
8
Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
9
Dept. of Medical Genetics, Medical University of Warsaw, Warsaw, Poland. Electronic address: rploski@wp.pl.

Abstract

POLG2 associated disorders belong to the group of mitochondrial DNA (mtDNA) diseases and present with a heterogeneous clinical spectrum, various age of onset, and disease severity. We report a 39-year old female presenting with childhood-onset and progressive neuroophthalmic manifestation with optic atrophy, mixed polyneuropathy, spinal and cerebellar ataxia and generalized chorea associated with mtDNA depletion. Whole-exome sequencing identified an ultra-rare homozygous missense mutation located at Chr17: 062474101-C > A (p.Asp433Tyr) in nuclear POLG2 gene encoding PolγB, an accessory subunits of mitochondrial polymerase γ responsible for mtDNA replication. The healthy parents and 2 sisters of the patient were heterozygous for the variant. To our best knowledge, this is the first case of homozygous variant in the POLG2 gene resulting in mitochondrial depletion syndrome in an adult patient and its clinical manifestations extend the clinical spectrum of POLG2 associated diseases.

KEYWORDS:

Ataxia; Chorea; Homozygous; Mitochondrial DNA depletion; Optic atrophy; POLG2; Polyneuropathy; Polγ; Premature ovarian failure

PMID:
31778857
DOI:
10.1016/j.ejmg.2019.103821

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