کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2812494 1569305 2006 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mutations in CABP4, the Gene Encoding the Ca2+-Binding Protein 4, Cause Autosomal Recessive Night Blindness
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی ژنتیک
پیش نمایش صفحه اول مقاله
Mutations in CABP4, the Gene Encoding the Ca2+-Binding Protein 4, Cause Autosomal Recessive Night Blindness
چکیده انگلیسی

Mutations in genes encoding either components of the phototransduction cascade or proteins presumably involved in signaling from photoreceptors to adjacent second-order neurons have been shown to cause congenital stationary night blindness (CSNB). Sequence alterations in CACNA1F lead to the incomplete type of CSNB (CSNB2), which can be distinguished by standard electroretinography (ERG). CSNB2 is associated with a reduced rod b-wave, a substantially reduced cone a-wave, and a reduced 30-Hz flicker ERG response. CACNA1F encodes the α1-subunit of an L-type Ca2+ channel (Cav1.4α), which is specific to photoreceptors and is present at high density in the synaptic terminals. Ten of our patients with CSNB2 showed no mutation in CACNA1F. To identify the disease-causing mutations, we used a candidate-gene approach. CABP4, a member of the calcium-binding protein (CABP) family, is located in photoreceptor synaptic terminals and is directly associated with the C-terminal domain of the Cav1.4α. Mice lacking either Cabp4 or Cav1.4α display a CSNB2-like phenotype. Here, we report for the first time that mutations in CABP4 lead to autosomal recessive CSNB. Our studies revealed homozygous and compound heterozygous mutations in two families. We also show that these mutations reduce the transcript levels to 30%–40% of those in controls. This suggests that the reduced amount of CABP4 is the reason for the signaling defect in these patients.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 79, Issue 4, October 2006, Pages 657–667
نویسندگان
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