New Genes Causing Hereditary Parkinson’s Disease or Parkinsonism

Puschmann, Andreas

doi:10.1007/s11910-017-0780-8

Cited by 89 publications

(76 citation statements)

References 88 publications

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“…Several genes are known to cause hereditary forms of Parkinson's disease (PD) or atypical parkinsonism . However, the genetic features of sub‐Saharan African (SSA) patients affected by these diseases remain undercharacterized .…”

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confidence: 99%

PTRHD1 Loss‐of‐function mutation in an african family with juvenile‐onset Parkinsonism and intellectual disability

et al. 2018

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Background: The genetic bases of PD in sub‐Saharan African (SSA) populations remain poorly characterized, and analysis of SSA families with PD might lead to the discovery of novel disease‐related genes. Objectives: To investigate the clinical features and identify the disease‐causing gene in a black South African family with 3 members affected by juvenile‐onset parkinsonism and intellectual disability. Methods: Clinical evaluation, neuroimaging studies, whole‐exome sequencing, homozygosity mapping, two‐point linkage analysis, and Sanger sequencing of candidate variants. Result: A homozygous 28‐nucleotide frameshift deletion in the PTRHD1 coding region was identified in the 3 affected family members and linked to the disease with genome‐wide significant evidence. PTRHD1 was recently nominated as the disease‐causing gene in two Iranian families, each containing 2 siblings with similar phenotypes and homozygous missense mutations. Conclusion: Together with the previous reports, we provide conclusive evidence that loss‐of‐function mutations in PTRHD1 cause autosomal‐recessive juvenile parkinsonism and intellectual disability. © 2018 International Parkinson and Movement Disorder Society

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confidence: 99%

PTRHD1 Loss‐of‐function mutation in an african family with juvenile‐onset Parkinsonism and intellectual disability

et al. 2018

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“…Andere atypischen Zeichen fanden sich nicht. Die Häufigkeit von DJ1-Mutationen wird um die 1% bei familiärem PS geschätzt (3).…”

Section: Monogenetische Ursachen Für Parkinson-syndromeunclassified

Seltene Parkinson-Syndrome

Ceballos-Baumann¹

2018

Nervenheilkunde

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ZusammenfassungDie verschiedenen Parkinson-Syndrome (PS) klinisch einzelnen Krankheitsentitäten zuzuordnen, gilt als schwierig. Es sind viele seltene Parkinson-Syndrome von dem häufigen sporadischen idiopathischen Parkinson-Syndrom (IPS) zu differenzieren. Zum Teil neu aufgelegte Kriterien für das IPS und die atypischen Parkinson-Syndrome wie Demenz vom Lewy-Body-Typ (DLB), Multisystematrophie (MSA), progressiver supranukleärer Blickparese (PSP) und kortikobasales Syndrom (CBS) sollten die diagnostische Einordnung verbessern. Patienten mit vom sporadischen IPS kaum unterscheidbaren monogenetischem PS, z. B. mit LRRK2-Mutationen oder mit einem Risikogen, z. B. Mutationen im GBAGen, können relativ einfach genetisch diagnostiziert werden. Bei jungen PS-Patienten müssen komplexe Krankheiten wie z. B. das häufige Mikrodeletionssyndrom 22q11.2 (Di-George-Syndrom), Morbus Wilson und “Morbus Fahr” sowie die Gruppe der Neurodegenerationen mit Eisenablagerung im Gehirn (NBIAs) berücksichtigt werden.

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“…Parkinson's disease (PD) is the second most common neurodegenerative disease (Calabrese, ). With technological advancement, a growing list of genes have been confirmed to cause familial PD (Deng, Wang, & Jankovic, ; Lill, ; Puschmann, ). Next‐generation sequencing technology has been applied worldwide to identify the causative genes for various neurological disorders (Bahassi & Stambrook, ).…”

Section: Introductionmentioning

confidence: 99%

POLG R964C and GBA L444P mutations in familial Parkinson's disease: Case report and literature review

et al. 2019

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Polymerase gamma ( POLG ) is an enzyme responsible for the replication and repair of mitochondrial DNA. Mutations in POLG may cause variable clinical manifestations, including parkinsonism, epilepsy, cerebellar ataxia, neuropathy, and progressive external ophthalmoplegia. However, mutations of this gene are rare in patients with typical Parkinson's disease (PD). We report a man (current age: 59 years) without any underlying disease presenting with right‐hand tremor at the age of 39 years, followed by slow movement, rigidity, and postural instability. He developed motor fluctuation and levodopa‐induced dyskinesia 8 years later. At the age of 58 years, cognitive decline and visual hallucination ensued; he was institutionalized thereafter. We used multiplex ligation‐dependent probe amplification, which demonstrated no large deletions or duplications of relevant PD genes. Next, targeted sequencing panel covering 51 genes causative for PD was applied for the proband; it revealed a heterozygous missense substitution R964C in POLG and a heterozygous missense substitution L444P in GBA . The patient's father, who had been diagnosed as having PD and type 2 diabetes mellitus at the age of 70 years, demonstrated identical mutations. This is the first report of familial PD combined with POLG R964C and GBA L444P mutations. Two pathogenic gene mutations potentially cause double hit in pathological neurodegeneration. This finding extends our understanding of the PD genotype–phenotype correlation.

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New Genes Causing Hereditary Parkinson’s Disease or Parkinsonism

Cited by 89 publications

References 88 publications

PTRHD1 Loss‐of‐function mutation in an african family with juvenile‐onset Parkinsonism and intellectual disability

PTRHD1 Loss‐of‐function mutation in an african family with juvenile‐onset Parkinsonism and intellectual disability

Seltene Parkinson-Syndrome

POLG R964C and GBA L444P mutations in familial Parkinson's disease: Case report and literature review

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