Transcranial sonography findings in a large family with homozygous and heterozygous PINK1 mutations

Objective: To investigate substantia nigra (SN) echogenicity in members of a family with homozygous and heterozygous PTEN induced kinase (PINK1) mutations with or without signs of Parkinson’s disease (PD). Methods: Transcranial sonography (TCS) was used to investigate 20 members of a family with PINK1 mutations, including four homozygous and 11 heterozygous mutation carriers and five individuals with no mutation. For comparison, a healthy control group of 18 subjects without a positive family history of PD (control group) and a healthy control group of 15 subjects with a positive family history of sporadic PD (relative group) were investigated. For statistical analysis, the larger area of the two SNs echogenicity (aSNmax) of each individual was selected. Results: A significantly increased aSNmax was found for all subgroups compared with the control group. The group of homozygous carriers of a PINK1 mutation had a significantly increased aSNmax compared with all of the other subgroups, except the group of heterozygous mutation carriers. Conclusions: These findings in carriers of a PINK1 mutation are comparable with those in carriers of Parkin mutations and non-genetic PD. The increased aSNmax in family members without a mutation suggests an additional contributing factor independent of the PINK1 mutation that may also play a role in relatives of patients with sporadic PD.

[1]  Houeto Jean-Luc.  [Parkinson's disease]. , 2022, La Revue du praticien.

[2]  G. Seidel,et al.  Substantia nigra hyperechogenicity correlates with clinical status and number of Parkin mutated alleles , 2007, Journal of Neurology.

[3]  A. Lang,et al.  Deciphering the role of heterozygous mutations in genes associated with parkinsonism , 2007, The Lancet Neurology.

[4]  J. Olzmann,et al.  PINK1 Protects against Oxidative Stress by Phosphorylating Mitochondrial Chaperone TRAP1 , 2007, PLoS biology.

[5]  D. Berg,et al.  Cross-sectional study discloses a positive family history for Parkinson’s disease and male gender as epidemiological risk factors for substantia nigra hyperechogenicity , 2007, Journal of Neural Transmission.

[6]  K. Reetz,et al.  Phenotypic spectrum of PINK1‐associated parkinsonism in 15 mutation carriers from 1 family , 2007, Movement disorders : official journal of the Movement Disorder Society.

[7]  N. Quinn,et al.  A heterozygous effect for PINK1 mutations in Parkinson's disease? , 2006, Annals of neurology.

[8]  P. Pramstaller,et al.  Heterozygous PINK1 mutations: A susceptibility factor for Parkinson disease? , 2006, Movement disorders : official journal of the Movement Disorder Society.

[9]  J. Volkmann,et al.  Recurrent LRRK2 (Park8) mutations in early‐onset Parkinson's disease , 2006, Movement disorders : official journal of the Movement Disorder Society.

[10]  J. Holton,et al.  PINK1 protein in normal human brain and Parkinson's disease. , 2006, Brain : a journal of neurology.

[11]  F. Binkofski,et al.  Clinical spectrum of homozygous and heterozygous PINK1 mutations in a large German family with Parkinson disease: role of a single hit? , 2006, Archives of neurology.

[12]  D. Berg,et al.  In vivo detection of iron and neuromelanin by transcranial sonography – a new approach for early detection of substantia nigra damage , 2006, Journal of Neural Transmission.

[13]  Klaus Fassbender,et al.  Transcranial sonography and [123I]FP-CIT SPECT disclose complementary aspects of Parkinson's disease. , 2006, Brain : a journal of neurology.

[14]  T. Nägele,et al.  Type and frequency of mutations in the LRRK2 gene in familial and sporadic Parkinson's disease*. , 2005, Brain : a journal of neurology.

[15]  R. Hilker,et al.  Lewy body Parkinson's disease in a large pedigree with 77 Parkin mutation carriers , 2005, Annals of neurology.

[16]  C. Klein,et al.  Early-onset parkinsonism associated with PINK1 mutations: Frequency, genotypes, and phenotypes , 2005, Neurology.

[17]  Christine Klein,et al.  Brain parenchyma sonography detects preclinical parkinsonism , 2004, Movement disorders : official journal of the Movement Disorder Society.

[18]  R. Nussbaum,et al.  Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1 , 2004, Science.

[19]  D W Dickson,et al.  Autosomal dominant parkinsonism associated with variable synuclein and tau pathology , 2004, Neurology.

[20]  D. Calne,et al.  Familial and sporadic Parkinson's disease usually display the same clinical features. , 2003, Parkinsonism & related disorders.

[21]  Klaus W. Lange,et al.  Echogenicity of the substantia nigra in relatives of patients with sporadic Parkinson’s disease , 2003, NeuroImage.

[22]  Paola Piccini,et al.  Clinical and subclinical dopaminergic dysfunction in PARK6‐linked parkinsonism: An 18F‐dopa PET study , 2002, Annals of neurology.

[23]  W. Gibb,et al.  The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[24]  J. Volkmann,et al.  Recurrent LRRK 2 ( Park 8 ) Mutations in Early-Onset Parkinson ’ s Disease , 2006 .

[25]  J. Holton,et al.  PINK 1 protein in normal human brain and Parkinson ’ s disease , 2006 .

[26]  U. Dillmann,et al.  SPECT disclose complementary aspects of Parkinson's disease , 2006 .