期刊
JOURNAL OF INHERITED METABOLIC DISEASE
卷 44, 期 6, 页码 1453-1462出版社
WILEY
DOI: 10.1002/jimd.12429
关键词
Batten disease; diagnosis; lysosomal disorders; natural history; neurodegenerative disease; neuronal ceroid lipofuscinosis
资金
- Batten Disease Support and Research Association
- Beyond Batten Disease Foundation
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [P50HD103536]
- National Institute of Neurological Disorders and Stroke [U01NS101946, K12NS066098, U54NS065768, R01NS060022]
- School of Medicine and Dentistry, University of Rochester
- Noah's Hope/Hope4Bridget
- Our Promise to Nicholas Foundation
A hierarchical diagnostic confidence scheme for CLN3 disease was developed based on genotype and phenotype data from an ongoing natural history study, with excellent face validity shown in a blinded reclassification study. The scheme included four major classes, with individuals further divided into subclasses based on phenotype within the Definite and Probable CLN3 disease classes. Test-retest reliability showed 96% agreement, providing a reliable basis for the diagnosis of CLN3 disease.
Over the past 20 years, diagnostic testing for genetic diseases has evolved, leading to variable diagnostic certainty for individuals included in long-term natural history studies. Using genotype and phenotype data from an ongoing natural history study of CLN3 disease, we developed a hierarchical diagnostic confidence scheme with three major classes: Definite, Probable, or Possible CLN3 disease. An additional level, CLN3 Disease PLUS, includes individuals with CLN3 disease plus an additional disorder with a separate etiology that substantially affects the phenotype. Within the Definite and Probable CLN3 disease classes, we further divided individuals into subclasses based on phenotype. After assigning participants to classes, we performed a blinded reclassification to assess the reliability of this scheme. A total of 134 individuals with suspected CLN3 disease were classified: 100 as Definite, 21 as Probable, and 7 as Possible. Six individuals were classified as CLN3-PLUS. Phenotypes included the classical juvenile-onset syndromic phenotype, a vision loss only phenotype, and an atypical syndromic phenotype. Some individuals were too young to fully classify phenotype. Test-retest reliability showed 96% agreement. We created a reliable diagnostic confidence scheme for CLN3 disease that has excellent face validity. This scheme has implications for clinical research in CLN3 and other rare genetic neurodegenerative disorders.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据