Dataset Information

The juvenile Batten disease protein, CLN3, and its role in regulating anterograde and retrograde post-Golgi trafficking.

ABSTRACT: Loss-of-function mutations in CLN3 are responsible for juvenile-onset neuronal ceroid lipofuscinosis (JNCL), or Batten disease, which is an incurable lysosomal disease that manifests with vision loss, followed by seizures and progressive neurodegeneration, robbing children of motor skills, speech and cognition, and eventually leading to death in the second or third decade of life. Emerging clinical evidence points to JNCL pathology outside of the CNS, including the cardiovascular system. The CLN3 gene encodes an unusual transmembrane protein, CLN3 or battenin, whose elusive function has been the subject of intense study for more than 10 years. Owing to the detailed characterization of a large number of disease models, our knowledge of CLN3 protein function is finally coming into focus. This review will describe the most current understanding of CLN3 structure, function and dysfunction in JNCL.

SUBMITTER: Cotman SL

PROVIDER: S-EPMC3334816 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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The juvenile Batten disease protein, CLN3, and its role in regulating anterograde and retrograde post-Golgi trafficking.

Cotman Susan L SL Staropoli John F JF

Clinical lipidology 20120201 1

Loss-of-function mutations in CLN3 are responsible for juvenile-onset neuronal ceroid lipofuscinosis (JNCL), or Batten disease, which is an incurable lysosomal disease that manifests with vision loss, followed by seizures and progressive neurodegeneration, robbing children of motor skills, speech and cognition, and eventually leading to death in the second or third decade of life. Emerging clinical evidence points to JNCL pathology outside of the CNS, including the cardiovascular system. The CLN ...[more]

PMID: 22545070

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Project description:PURPOSE:To characterize the retinal phenotype of juvenile neuronal ceroid lipofuscinosis (JNCL), highlight delayed and mistaken diagnosis, and propose an algorithm for early identification. DESIGN:Retrospective case series. PARTICIPANTS:Eight children (5 female) with JNCL. METHODS:Review of clinical notes, retinal imaging including fundus autofluorescence and OCT, electroretinography (ERG), and both microscopy and molecular genetic testing. MAIN OUTCOME MEASUREMENTS:Demographic data, signs and symptoms, visual acuity (VA), fundus autofluorescence and OCT findings, ERG phenotype, and microscopy/molecular genetics. RESULTS:Participants presented with rapid bilateral vision loss over 1 to 18 months, with mean VA deteriorating from 0.44 logarithm of the minimum angle of resolution (logMAR) (range, 0.20-1.78 logMAR) at baseline to 1.34 logMAR (0.30 logMAR - light perception) at last follow-up. Age of onset ranged from 3 to 7 years (mean, 5.3 years). The age at diagnosis of JNCL ranged from 7 to 10 years (mean, 8.3 years). Six children displayed eccentric fixation, and 6 children had cognitive or neurologic signs at the time of diagnosis (75%). Seven patients had bilateral bull's-eye maculopathy at presentation. Coats-like exudative vasculopathy, not previously reported in JNCL, was observed in 1 patient. OCT imaging revealed near complete loss of outer retinal layers and marked atrophy of the nerve fiber and ganglion cell layers at the central macula. An electronegative ERG was present in 4 patients (50%), but with additional a-wave reduction, there was an undetectable ERG in the remaining 4 patients. Blood film microscopy revealed vacuolated lymphocytes, and electron microscopy showed lysosomal (fingerprint) inclusions in all 8 patients. CONCLUSIONS:In a young child with bilateral rapidly progressive vision loss and macular disturbance, blood film microscopy to detect vacuolated lymphocytes is a rapid, readily accessible, and sensitive screening test for JNCL. Early suspicion of JNCL can be aided by detailed directed history and high-resolution retinal imaging, with subsequent targeted microscopy/genetic testing. Early diagnosis is critical to ensure appropriate management, counseling, support, and social care for children and their families. Furthermore, although potential therapies for this group of disorders are in early-phase clinical trial, realistic expectations are that successful intervention will be most effective when initiated at the earliest stage of disease.

Dataset Information

The juvenile Batten disease protein, CLN3, and its role in regulating anterograde and retrograde post-Golgi trafficking.

Publications

The juvenile Batten disease protein, CLN3, and its role in regulating anterograde and retrograde post-Golgi trafficking.

Similar Datasets

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