Paulo Ribeiro Nóbrega , Anderson Rodrigues Brandão Paiva , Antonio Duarte Amorim Junior , Pedro Lucas Grangeiro Sá Barreto Lima , Katiane Sayão Souza Cabral , Isabella Peixoto Barcelos , André Luis Santos Pessoa , Carlos Frederico Leite Souza-Lima , Matheus Augusto Araújo Castro , Fernando Freua , Emerson de Santana Santos , Margleice Marinho Vieira Rocha , Rayana Elias Maia , Rodrigo Santos Araújo , Juan David Guevara Ramos , Rosane Guazi Resende , Gerson da Silva Carvalho , Luciana Patrizia Andrade Valença , José Ronaldo Lima de Carvalho Jr. , Eduardo Sousa Melo , David S. Lynch
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引用次数: 0
Abstract
Purpose
Ceroid lipofuscinosis type 11 (CLN11) is a very rare disease, being reported in only 13 unrelated families so far. Further reports are necessary to comprehend the clinical phenotype of this condition. This article aims to report 9 additional cases of CLN11 from 9 unrelated Latin American families presenting with relatively slow disease progression.
Methods
This was a retrospective observational study including patients with CLN11. Patients were identified through an active search for granulin precursor gene (GRN) pathogenic variants across the entire database of next-generation sequencing of a commercial laboratory and by contacting attending physicians to check for clinical and radiologic findings compatible with a neuronal ceroid lipofuscinosis phenotype.
Results
Nine CLN11 patients from unrelated families were evaluated. Age of onset varied between 3 to 17 years. The most common findings were visual impairment, cerebellar ataxia, seizures, myoclonus, and cognitive decline. One patient had a previously unreported finding of cervical, perioral, and tongue myoclonus. Most of the patients were able to walk unassisted after an average of 14.2 years (SD 4.76 y) from disease onset.
Conclusion
We describe 9 new cases of a very rare type of neuronal ceroid lipofuscinosis (CLN11) from Latin America with a recurrent p.(Gln257ProfsTer27) and a novel p.(Cys83Ter) nonsense variant. Our findings suggest that a slowly progressive neuronal ceroid lipofuscinosis might be a clue for the diagnosis of CLN11.
期刊介绍:
Genetics in Medicine (GIM) is the official journal of the American College of Medical Genetics and Genomics. The journal''s mission is to enhance the knowledge, understanding, and practice of medical genetics and genomics through publications in clinical and laboratory genetics and genomics, including ethical, legal, and social issues as well as public health.
GIM encourages research that combats racism, includes diverse populations and is written by authors from diverse and underrepresented backgrounds.