Mutations in ABCA4 result in accumulation of lipofuscin before slowing of the retinoid cycle: a reappraisal of the human disease sequence

来自 EBSCO

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作者：

AV Cideciyan，TS Aleman，S Malgorzata，SB Schwartz，JD Steinberg，AJ Brucker，AM Maguire，B Jean，EM Stone，SG Jacobson

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摘要：

Mutations in , which encodes a photoreceptor specific ATP-cassette transporter (), cause autosomal recessive forms of blindness due to (RD) including Stargardt disease. The exact disease sequence leading to photoreceptor and loss in -RD is not known. Extrapolation from and in vitro studies predicts that two of the earliest pathophysiological features resulting from disturbed function in would be slowed kinetics of the cycle and accelerated deposition of lipofuscin in the retinal pigment epithelium (). To determine the pathogenetic sequence, we studied surrogate measures of cycle kinetics, , and rod and cone photoreceptor and loss in -RD patients with a wide spectrum of disease severities. There were different extents of photoreceptor/loss and in different regions of the . Slowing of cycle kinetics was not present in all patients; when present, it was not homogeneous across the ; and the extent of slowing correlated well with the degree of degeneration. The orderly relationship between these phenotypic features permitted the development of a model of disease sequence in -RD. The model predicted as a key and early component of the disease expression in , as in . In , however, abnormal slowing of the rod and cone cycle occurs at later stages of the disease sequence. Knowledge of the disease sequence will be critical for defining rates of progression, selecting appropriate patients and retinal locations for future therapy, and choosing appropriate treatment outcomes.

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关键词：

galectin-1 galectin-3 galectin-7 quaternary structures

DOI：

10.1093/hmg/ddh048

被引量：

365

年份：

2004