Perry syndrome: Novel DCTN1 mutation in a large kindred and first observation of prodromal disease.
Parkinsonism Relat Disord
; 112: 105481, 2023 Jul.
Article
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| MEDLINE
| ID: mdl-37336025
ABSTRACT
INTRODUCTION:
Perry syndrome (PS) is a hereditary neurodegenerative disorder caused by mutations in the DCTN1 gene and characterized by TDP-43 pathology. As the diagnosis is usually made at the advanced stages of the disease, there are no studies on the asymptomatic mutation carriers and their conversion to overt disease.METHODS:
We personally examined 27 members of the large kindred of 104 individuals with familial parkinsonism. We evaluated each case with clinical (neurological examination; motor and non-motor scales), genetic testing (whole-exome or Sanger sequencing), and laboratory (neurofilament light, NFL; glial fibrillary acidic protein, GFAP) measures. Autopsy study was done on two individuals.RESULTS:
The mean age at evaluation was 49 years. Comorbidities were present in 20 cases, including sleep problems (n = 15 total, sleep apnea in 7), dysautonomia (n = 10), weight loss (n = 8), and anxiety/depression (n = 8). Neurological abnormalities were present in 18, including parkinsonism (n = 7), isolated tremor (n = 2), and varied isolated signs in individual cases. Cognition and smell were preserved. Genetic testing revealed a novel c.200G > T (Gly67Val) mutation in the DCTN1 gene in 10 individuals. The mutation, segregated with the PS phenotype (n = 4), was absent in gnomAD, and in silico predictions indicated it was pathogenic. Three young mutation carriers were monosymptomatic (prodromal), and three were asymptomatic. Plasma NFL and GFAP values were similar among the cases. Autopsy studies showed typical PS neuropathological findings.CONCLUSIONS:
We identified a novel pathogenic Gly67Val DCTN1 mutation. We report prodromal disease of PS in some mutation carriers; however, more investigation is necessary to confirm this observation.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trastornos Parkinsonianos
/
Depresión
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Parkinsonism Relat Disord
Asunto de la revista:
NEUROLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Polonia