Novel triple missense mutations of GUCY2D gene in Japanese family with cone-rod dystrophy

Possible use of genotyping microarray

Shigeo Yoshida, Yoko Yamaji, Ayako Yoshida, Rumi Kuwahara, Ken Yamamoto, Toshiaki Kubata, Tatsuro Ishibashi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Purpose: To report a novel mutation in the GUCY2D gene in a Japanese family with autosomal dominant cone-rod dystrophy (adCORD), and to examine the possible use of arrayed primer extension (APEX)-based genotyping chip in detecting mutations. Methods: Genomic DNA was extracted from the peripheral blood of family members with adCORD. It was PCR-amplified, fragmented, and hybridized to APEX-based genotyping microarrays on which known disease-associated sequence variations were arrayed for patients with early-onset retinal dystrophy. All coding exons of the GUCY2D gene were directly sequenced. The PCR amplicon carrying a novel mutation was subcloned, and each clone was sequenced. Results: Five single nucleotide polymorphisms in AIPL1, RPGRIP1, and GUCY2D were detected in the proband by microarray screening, and all were validated by direct sequencing. A novel heterozygous triple missense mutation of c.2540_2542delinsTCC (p.Gln847_Lys848delinsLeuGln amino acid substitutions) was found in both the proband and his father, and the three nucleotide changes were located on the same chromosome. Electroretinography (ERGs) demonstrated a significant reduction in rod function and a complete absence of cone function in both affected individuals. Conclusions: A novel heterozygous triple consecutive missense mutation in the GUCY2D gene has been linked to adCORD. Our study demonstrates that the APEX-based gene screening can be used to identify simultaneously disease-modifying sequence changes as well as disease-causing mutations, once proper and comprehensive sites of sequence variations of the disease are arrayed.

Original languageEnglish
Pages (from-to)1558-1564
Number of pages7
JournalMolecular Vision
Volume12
Publication statusPublished - Dec 6 2006

Fingerprint

Missense Mutation
Mutation
Genes
Retinal Dystrophies
Electroretinography
Polymerase Chain Reaction
Amino Acid Substitution
Fathers
Single Nucleotide Polymorphism
Exons
Nucleotides
Clone Cells
Chromosomes
Cone-Rod Dystrophies
DNA
Retinal Cone Dystrophy 1

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Novel triple missense mutations of GUCY2D gene in Japanese family with cone-rod dystrophy : Possible use of genotyping microarray. / Yoshida, Shigeo; Yamaji, Yoko; Yoshida, Ayako; Kuwahara, Rumi; Yamamoto, Ken; Kubata, Toshiaki; Ishibashi, Tatsuro.

In: Molecular Vision, Vol. 12, 06.12.2006, p. 1558-1564.

Research output: Contribution to journalArticle

Yoshida, S, Yamaji, Y, Yoshida, A, Kuwahara, R, Yamamoto, K, Kubata, T & Ishibashi, T 2006, 'Novel triple missense mutations of GUCY2D gene in Japanese family with cone-rod dystrophy: Possible use of genotyping microarray', Molecular Vision, vol. 12, pp. 1558-1564.
Yoshida S, Yamaji Y, Yoshida A, Kuwahara R, Yamamoto K, Kubata T et al. Novel triple missense mutations of GUCY2D gene in Japanese family with cone-rod dystrophy: Possible use of genotyping microarray. Molecular Vision. 2006 Dec 6;12:1558-1564.
Yoshida, Shigeo ; Yamaji, Yoko ; Yoshida, Ayako ; Kuwahara, Rumi ; Yamamoto, Ken ; Kubata, Toshiaki ; Ishibashi, Tatsuro. / Novel triple missense mutations of GUCY2D gene in Japanese family with cone-rod dystrophy : Possible use of genotyping microarray. In: Molecular Vision. 2006 ; Vol. 12. pp. 1558-1564.
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