A Clinicopathologic Entity

Results: Presenting signs in the parkin disease cases were hand or leg tremor often combined with dystonia. Mean age at onset was 34 years; all cases were compound heterozygous for mutations of parkin. Freezing of gait, postural deformity, and motor fluctuations were common late features. No patients had any evidence of cognitive impairment or dementia. Neuronal counts in the substantia nigra pars compacta revealed that neuronal loss in the parkin cases was as severe as that seen in PD, but relative preservation of the dorsal tier was seen in comparison with PD (P=.04). Mild neuronal loss was identified in the locus coeruleus and dorsal motor nucleus of the vagus, but not in the nucleus basalis of Meynert, raphe nucleus, or other brain regions. Sparse Lewy bodies were identified in 2 cases (brainstem and cortex).

[1]  Y. Shimo,et al.  Lewy body pathology in a patient with a homozygous Parkin deletion , 2013, Movement disorders : official journal of the Movement Disorder Society.

[2]  O. Levy,et al.  The neuropathology of genetic Parkinson's disease , 2012, Movement disorders : official journal of the Movement Disorder Society.

[3]  J. Hardy,et al.  Widespread Lewy body and tau accumulation in childhood and adult onset dystonia-parkinsonism cases with PLA2G6 mutations , 2012, Neurobiology of Aging.

[4]  J. Yun,et al.  Phenotype analysis in patients with early onset Parkinson’s disease with and without parkin mutations , 2011, Journal of Neurology.

[5]  P. Pástor,et al.  PINK1-linked parkinsonism is associated with Lewy body pathology. , 2010, Brain : a journal of neurology.

[6]  J. Ahlskog.  Parkin and PINK1 parkinsonism may represent nigral mitochondrial cytopathies distinct from Lewy body Parkinson's disease. , 2009, Parkinsonism & related disorders.

[7]  N. Wood,et al.  Cell death pathways in Parkinson's disease: role of mitochondria. , 2009, Antioxidants & redox signaling.

[8]  F. Schmitt,et al.  Lewy Body Pathology in Normal Elderly Subjects , 2009, Journal of neuropathology and experimental neurology.

[9]  V. Hristova,et al.  Identification of a Novel Zn2+-binding Domain in the Autosomal Recessive Juvenile Parkinson-related E3 Ligase Parkin* , 2009, Journal of Biological Chemistry.

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

[11]  N. Hattori,et al.  Preserved cardiac sympathetic nerve accounts for normal cardiac uptake of MIBG in PARK2 , 2005, Movement disorders : official journal of the Movement Disorder Society.

[12]  K. Lim,et al.  Familial-associated mutations differentially disrupt the solubility, localization, binding and ubiquitination properties of parkin. , 2005, Human molecular genetics.

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

[14]  Janel O. Johnson,et al.  Parkin disease in a Brazilian kindred: Manifesting heterozygotes and clinical follow‐up over 10 years , 2005, Movement disorders : official journal of the Movement Disorder Society.

[15]  Niall P Quinn,et al.  The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multiple system atrophy: clinicopathological correlations. , 2004, Brain : a journal of neurology.

[16]  M. Iwata,et al.  Parkin-positive autosomal recessive juvenile parkinsonism with α-synuclein-positive inclusions , 2004, Neurology.

[17]  N. Quinn,et al.  Olfaction differentiates parkin disease from early-onset parkinsonism and Parkinson disease , 2004, Neurology.

[18]  P. Lockhart,et al.  RING finger 1 mutations in Parkin produce altered localization of the protein. , 2003, Human molecular genetics.

[19]  N. Hattori,et al.  Autosomal recessive parkinsonism linked to parkin gene in a Tunisian family. Clinical, genetic and pathological study. , 2003, Parkinsonism & related disorders.

[20]  Nicholas W Wood,et al.  Parkin disease: a phenotypic study of a large case series. , 2003, Brain : a journal of neurology.

[21]  H. Braak,et al.  Staging of brain pathology related to sporadic Parkinson’s disease , 2003, Neurobiology of Aging.

[22]  N. Hattori,et al.  Genotype–phenotype correlation: Familial Parkinson disease , 2003, Neuropathology : official journal of the Japanese Society of Neuropathology.

[23]  Nicola Pavese,et al.  Progression of nigrostriatal dysfunction in a parkin kindred: an [18F]dopa PET and clinical study. , 2002, Brain : a journal of neurology.

[24]  L. Seeberger,et al.  Linkage stratification and mutation analysis at the parkin locus identifies mutation positive Parkinson's disease families , 2002, Journal of medical genetics.

[25]  D. Hernandez,et al.  Lewy bodies and parkinsonism in families with parkin mutations , 2001, Annals of neurology.

[26]  H. Soininen,et al.  α‐Synuclein pathology is highly dependent on the case selection , 2001, Neuropathology and applied neurobiology.

[27]  N. Quinn,et al.  Clinical and pathologic abnormalities in a family with parkinsonism and parkin gene mutations , 2001, Neurology.

[28]  X. Breakefield,et al.  Parkin deletions in a family with adult‐onset, tremor‐dominant parkinsonism: Expanding the phenotype , 2000, Annals of neurology.

[29]  T. Kondo,et al.  Pathologic and biochemical studies of juvenile parkinsonism linked to chromosome 6q , 1998, Neurology.

[30]  Y. Mizuno,et al.  Clinical, pathologic and genetic studies on autosomal recessive early-onset parkinsonism with diurnal fluctuation. , 1998, Parkinsonism & related disorders.

[31]  S. Minoshima,et al.  Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism , 1998, Nature.

[32]  A A Schäffer,et al.  Localization of a gene for an autosomal recessive form of juvenile Parkinsonism to chromosome 6q25.2-27. , 1997, American journal of human genetics.

[33]  J. Rinne,et al.  Cell counts in the substantia nigra: a comparison of single section counts and disector counts in patients with Parkinson's disease and in controls , 1995, Neuropathology and applied neurobiology.

[34]  A. Lees,et al.  Ageing and Parkinson's disease: substantia nigra regional selectivity. , 1991, Brain : a journal of neurology.

[35]  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.

[36]  H. Parker,et al.  Enteroscopy and small bowel biopsy utilizing a peroral colonoscope. , 1983, Gastrointestinal endoscopy.

[37]  M. Tada,et al.  Pediatric enteroscopy with a sonde-type small intestinal fiberscope (SSIF-type VI). , 1983, Gastrointestinal endoscopy.

[38]  K. Ogoshi,et al.  New technic for small intestinal fiberoscopy. , 1973, Gastrointestinal endoscopy.

[39]  M. Cookson,et al.  Genetic neuropathology of Parkinson's disease. , 2008, International journal of clinical and experimental pathology.

[40]  G. Halliday.  Substantia Nigra and Locus Coeruleus , 2004 .