Nóbrega Paulo Ribeiro, Paiva Anderson Rodrigues Brandão, Amorim Junior Antonio Duarte, Lima Pedro Lucas Grangeiro Sá Barreto, Cabral Katiane Sayão Souza, Barcelos Isabella Peixoto, Pessoa André Luis Santos, Souza-Lima Carlos Frederico Leite, Castro Matheus Augusto Araújo, Freua Fernando, Santos Emerson de Santana, Rocha Margleice Marinho Vieira, Maia Rayana Elias, Araújo Rodrigo Santos, Ramos Juan David Guevara, Resende Rosane Guazi, Carvalho Gerson da Silva, Valença Luciana Patrizia Andrade, Lima de Carvalho José Ronaldo, Melo Eduardo Sousa, Pedroso José Luiz, Barsottini Orlando Graziani Povoas, Houlden Henry, Kok Fernando, Lynch David S
Division of Neurology, Universidade Federal do Ceara, Fortaleza, CE, Brazil; Centro Universitário Christus, Fortaleza, CE, Brazil.
Neurogenetics Unit, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil; Mendelics Genomic Analysis, São Paulo, SP, Brazil.
Genet Med. 2025 Jan;27(1):101291. doi: 10.1016/j.gim.2024.101291. Epub 2024 Oct 9.
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.
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.
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.
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.
11型蜡样脂褐质沉积病（CLN11）是一种非常罕见的疾病，迄今为止仅在13个无亲缘关系的家族中有报道。需要更多报道来了解这种疾病的临床表型。本文旨在报告来自9个无亲缘关系的拉丁美洲家族的另外9例CLN11病例，这些病例疾病进展相对缓慢。
这是一项回顾性观察研究，纳入了CLN11患者。通过在商业实验室的整个下一代测序数据库中积极搜索颗粒蛋白前体基因（GRN）的致病变异，并联系主治医生检查是否有与神经元蜡样脂褐质沉积病表型相符的临床和放射学表现，来确定患者。
对来自无亲缘关系家族的9例CLN11患者进行了评估。发病年龄在3至17岁之间。最常见的表现为视力障碍、小脑共济失调、癫痫发作、肌阵挛和认知衰退。1例患者有先前未报道的颈部、口周和舌肌阵挛表现。大多数患者在疾病发作后平均14.2年（标准差4.76年）仍能独立行走。
我们描述了来自拉丁美洲的9例非常罕见的神经元蜡样脂褐质沉积病（CLN11）新病例，存在复发性的p.（Gln257ProfsTer27）和一种新发现的p.（Cys83Ter）无义变异。我们的研究结果表明，缓慢进展的神经元蜡样脂褐质沉积病可能是诊断CLN11的一个线索。
