Molecular Diagnosis of 34 Japanese Families with Leber Congenital Amaurosis Using Targeted Next Generation Sequencing

Scientific Reports
Katsuhiro HosonoYoshihiro Hotta

Abstract

Leber congenital amaurosis (LCA) is a genetically and clinically heterogeneous disease, and represents the most severe form of inherited retinal dystrophy (IRD). The present study reports the mutation spectra and frequency of known LCA and IRD-associated genes in 34 Japanese families with LCA (including three families that were previously reported). A total of 74 LCA- and IRD-associated genes were analysed via targeted-next generation sequencing (TS), while recently discovered LCA-associated genes, as well as known variants not able to be screened using this approach, were evaluated via additional Sanger sequencing, long-range polymerase chain reaction, and/or copy number variation analyses. The results of these analyses revealed 30 potential pathogenic variants in 12 (nine LCA-associated and three other IRD-associated) genes among 19 of the 34 analysed families. The most frequently mutated genes were CRB1, NMNAT1, and RPGRIP1. The results also showed the mutation spectra and frequencies identified in the analysed Japanese population to be distinctly different from those previously identified for other ethnic backgrounds. Finally, the present study, which is the first to conduct a NGS-based molecular diagnosis of a large Japane...Continue Reading

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Citations

Mar 29, 2019·International Journal of Molecular Sciences·Kentaro KurataYoshihiro Hotta
Sep 3, 2020·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Kaoru FujinamiUNKNOWN Japan Eye Genetics Consortium Study Group
Nov 2, 2019·Human Genome Variation·Daisuke MiyamichiNoriyuki Azuma
Aug 22, 2020·Translational Vision Science & Technology·Xiao LiuUNKNOWN Japan Eye Genetics Consortium
Mar 29, 2020·American Journal of Medical Genetics. Part a·Takaaki HayashiYoshihiro Hotta
Oct 20, 2020·Frontiers in Bioengineering and Biotechnology·Fang-Yuan HuJi-Hong Wu
Mar 12, 2021·BMC Medical Genomics·Dae Joong MaHyeong Gon Yu
Oct 23, 2019·Experimental Eye Research·Altaf A Kondkar, Khaled K Abu-Amero
May 29, 2021·Experimental Eye Research·Zhen YiQingjiong Zhang

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Methods Mentioned

BETA
PCR
exome sequencing

Software Mentioned

GATK HaplotypeCaller
Burrows
CADD
cutadapt
Thermal Cycler Dice Real Time System
Genome Analysis Toolkit ( GATK
Wheeler Aligner
ANNOVAR

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