Perry Disease: Expanding the Genetic Basis

Dulski, Jarosław; Koga, Shunsuke; Liberski, Paweł P.; Sitek, Emilia J.; Butala, Ankur; Sławek, Jarosław; Dickson, Dennis W.; Wszołek, Zbigniew K.

doi:10.1002/mdc3.13764

Cited by 4 publications

(3 citation statements)

References 21 publications

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“…The first case was identified in a female patient without a family history of PS. The variant was demonstrated to be pathogenic based on the clinical features and autopsy findings ( 32 ). The second was a 65-year-old female patient who presented with difficulties in falling asleep and personality changes that progressed over four years.…”

Section: Discussionmentioning

confidence: 99%

First family with Perry syndrome from Mexico

Flores‑Lagunes,

Del Pozo‑Yauner,

Carrillo‑Sánchez

et al. 2024

Biomed Rep

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Perry syndrome (PS) is a rare autosomal dominant disease characterized by parkinsonism, central hypoventilation, weight loss and depression and is caused by pathogenic mutations in the dynactin subunit 1 ( DCTN1 ) gene (encoding p150 glued protein). To date, only two cases have been reported in Latin America, specifically in Colombia and Argentina. The present study, to the best of our knowledge, reports the first recorded Mexican family with PS. The clinical features of the proband and a family history of early parkinsonism led to the suspicion of PS. The pathogenic variant NM_004082:c.212G>A, causing a (p.Gly71Glu) mutation in the p150 glued protein, was identified in exon 2 of the DCTN1 gene by exome sequencing, confirming the diagnosis of PS. (p.Gly71Glu) has been previously identified in at least 4 cases of PS from different ethnic backgrounds. Genetic counseling was provided to the available family members. To clarify the impact of the (p.Gly71Glu) variant on the structure and function of the cytoskeleton-associated protein Gly rich (CAP-Gly) domain of p150 glued , Glu71 mutated CAP-Gly domains were modeled and compared with the wild-type. It was hypothesized that the larger and more charged side chain of Glu may induce conformational and electrostatic changes, imposing a conformational restriction on the peptide backbone that would affect interaction with the p150 glued protein partners, causing dysfunction in the dynactin protein complex.

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Section: Discussionmentioning

confidence: 99%

First family with Perry syndrome from Mexico

Flores‑Lagunes,

Del Pozo‑Yauner,

Carrillo‑Sánchez

et al. 2024

Biomed Rep

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“…The pathological features of Perry disease have revealed substantial neuronal loss and gliosis, with few or no Lewy bodies or neurofibrillary tangles present in the substantia nigra [4,6,7,[17][18][19][20][21][22][23]. Neuronal loss is detected in the lentiform nucleus, the locus coeruleus, the dorsal raphe nucleus, the periaqueductal gray matter, the hypothalamus, and the brainstem, including putative respiratory neurons in the medulla [6,20,21,24].…”

Section: Pathology Of Perry Diseasementioning

confidence: 99%

“…The CAP-Gly and basic domains have microtubule binding affinity [60][61][62][63]. Most mutations in Perry disease are located within CAP-Gly domains [8,23,[64][65][66][67][68][69][70]. Importantly, a DCTN1 mutation (p.G59S mutation) causes HMN7B [25,26,71] (Figure 2).…”

Section: Expansion Of Dctn1 Mutationsmentioning

confidence: 99%

Perry Disease: Bench to Bedside Circulation and a Team Approach

Mishima,

Yuasa-Kawada,

Fujioka

et al. 2024

Biomedicines

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With technological applications, especially in genetic testing, new diseases have been discovered and new disease concepts have been proposed in recent years; however, the pathogenesis and treatment of these rare diseases are not as well established as those of common diseases. To demonstrate the importance of rare disease research, in this paper we focus on our research topic, Perry disease (Perry syndrome). Perry disease is a rare autosomal dominant neurodegenerative disorder clinically characterized by parkinsonism, depression/apathy, weight loss, and respiratory symptoms including central hypoventilation and central sleep apnea. The pathological classification of Perry disease falls under TAR DNA-binding protein 43 (TDP-43) proteinopathies. Patients with Perry disease exhibit DCTN1 mutations, which is the causative gene for the disease; they also show relatively uniform pathological and clinical features. This review summarizes recent findings regarding Perry disease from both basic and clinical perspectives. In addition, we describe technological innovations and outline future challenges and treatment prospects. We discuss the expansion of research from rare diseases to common diseases and the importance of collaboration between clinicians and researchers. Here, we highlight the importance of researching rare diseases as it contributes to a deeper understanding of more common diseases, thereby opening up new avenues for scientific exploration.

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Understanding Parkinson disease in Spain: Genetic and clinical insights

Gómez‐Garre,

Martín‐Bórnez,

Muñoz‐Delgado

et al. 2024

Euro J of Neurology

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Background and purposeParkinson disease (PD) is a complex and heterogeneous neurodegenerative disorder with a broad spectrum of clinical manifestations, determined by a complex interplay of environmental and genetic factors. This study aimed to investigate genetic variants associated with PD and assess their impact on the disease phenotype through genotype–phenotype correlations.MethodsWe employed a targeted resequencing panel to analyze 27 genes linked to PD in a cohort of 1185 PD patients from southern Spain. Variants were categorized based on the American College of Medical Genetics and Genomics pathogenicity criteria. Demographic and clinical data were also collected.ResultsAmong the patients analyzed, 13.5% carried potential disease‐causing pathogenic or likely pathogenic variants in 12 different genes, indicating significant genetic heterogeneity. The most frequently affected genes were LRRK2, PRKN, and GBA1 (accounting for 72.1% of positive cases). Sex‐specific differences were observed, with a higher proportion of female patients carrying LRRK2 variants. Differences in age at onset and clinical features were also observed among the different mutated genes. Notably, variants in genes associated with atypical parkinsonism presented distinct clinical presentations, highlighting the importance of genetic factors in the differential diagnosis.ConclusionsOur study provides valuable information on the genetic landscape of PD and its clinical manifestations. The observed genotype–phenotype correlations, along with sex‐specific differences, emphasize the complexity of PD pathogenesis, underlining the importance of personalized approaches to PD diagnosis and treatment. Further investigations into genetic interactions and population‐specific effects are warranted to enhance our understanding of PD etiology and improve patient care.

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Perry Disease: Expanding the Genetic Basis

Cited by 4 publications

References 21 publications

First family with Perry syndrome from Mexico

First family with Perry syndrome from Mexico

Perry Disease: Bench to Bedside Circulation and a Team Approach

Understanding Parkinson disease in Spain: Genetic and clinical insights

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