Rare compound heterozygous variants in PNKP identified by whole exome sequencing in a German patient with ataxia-oculomotor apraxia 4 and pilocytic astrocytoma

Clinical Genetics
C ScholzW Hofmann

Abstract

Ataxia-oculomotor apraxia type 4 (AOA4) is a rare autosomal recessive neurologic disorder. The phenotype is characterized by ataxia, oculomotor apraxia, peripheral neuropathy and dystonia. AOA4 is caused by biallelic pathogenic variants in the PNKP gene encoding a polynucleotide kinase 3'-phosphatase with an important function in DNA-damage repair. By whole exome sequencing, we identified 2 variants within the PNKP gene in a 27-year-old German woman with a clinical AOA phenotype combined with a cerebellar pilocytic astrocytoma diagnosed at 23 years of age. One variant, a duplication in exon 14 resulting in the frameshift c.1253_1269dup p.(Thr424fs*49), has previously been described as pathogenic, for example, in cases of AOA4. The second variant, representing a nonsense mutation in exon 17, c.1545C>G p.(Tyr515*), has not yet been described and is predicted to cause a loss of the 7 C-terminal amino acids. This is the first description of AOA4 in a patient with central European descent. Furthermore, the occurrence of a pilocytic astrocytoma has not been described before in an AOA4 patient. Our data demonstrate compound heterozygous PNKP germline variants in a German patient with AOA4 and provide evidence for a possible link with ...Continue Reading

References

Mar 8, 2005·Molecular Cell·Nina K BernsteinJ N Mark Glover
Jul 3, 2013·Nature Genetics·David T W JonesUNKNOWN International Cancer Genome Consortium PedBrain Tumor Project
Mar 3, 2015·American Journal of Human Genetics·Jose BrasRita Guerreiro
Apr 12, 2016·Neurology. Genetics·Martin PaucarAnn Nordgren

❮ Previous
Next ❯

Citations

Jun 7, 2019·Journal of Neurology, Neurosurgery, and Psychiatry·Stefano C PrevitaliAlessandra Bolino
May 22, 2019·Translational Neurodegeneration·Luis Bermúdez-Guzmán, Alejandro Leal
Feb 3, 2021·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Hacer DurmusYesim Parman
Sep 10, 2021·Journal of Neurology·Nataša Dragašević-MiškovićVladimir S Kostić

❮ Previous
Next ❯

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Ataxias (MDS)

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Ataxias

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on different types of ataxias here.

Ataxia

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.