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

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21 Citations (Scopus)


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
Publication statusPublished - Dec 6 2006

All Science Journal Classification (ASJC) codes

  • Ophthalmology


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