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. 2018:1074:219-228.
doi: 10.1007/978-3-319-75402-4_27.

Whole-Exome Sequencing Identifies Novel Variants that Co-segregates with Autosomal Recessive Retinal Degeneration in a Pakistani Pedigree

Pooja Biswas  1 , Muhammad Asif Naeem  2 , Muhammad Hassaan Ali  3 , Muhammad Zaman Assir  3 , Shaheen N Khan  2 , Sheikh Riazuddin  2   3   4 , J Fielding Hejtmancik  5 , S Amer Riazuddin  6 , Radha Ayyagari  7
Affiliations

Whole-Exome Sequencing Identifies Novel Variants that Co-segregates with Autosomal Recessive Retinal Degeneration in a Pakistani Pedigree

Pooja Biswas et al. Adv Exp Med Biol. 2018.

Abstract

Purpose: To identify the molecular basis of inherited retinal degeneration (IRD) in a familial case of Pakistani origin using whole-exome sequencing.

Methods: A thorough ophthalmic examination was completed, and genomic DNA was extracted using standard protocols. Whole exome(s) were captured with Agilent V5 + UTRs probes and sequenced on Illumina HiSeq genome analyzer. The exomeSuite software was used to filter variants, and the candidate causal variants were prioritized, examining their allele frequency and PolyPhen2, SIFT, and MutationTaster predictions. Sanger dideoxy sequencing was performed to confirm the segregation with disease phenotype and absence in ethnicity-matched control chromosomes.

Results: Ophthalmic examination confirmed retinal degeneration in all affected individuals that segregated as an autosomal recessive trait in the family. Whole-exome sequencing identified two homozygous missense variants: c.1304G > A; p.Arg435Gln in ZNF408 (NM_024741) and c.902G > A; p.Gly301Asp in C1QTNF4 (NM_031909). Both variants segregated with the retinal phenotype in the PKRD320 and were absent in ethnically matched control chromosomes.

Conclusion: Whole-exome sequencing coupled with bioinformatics analysis identified potential novel variants that might be responsible for IRD.

Keywords: C1QTNF4; Novel variants; Retinal degeneration; Whole-exome sequencing; ZNF408.

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Figures

Fig. 27.1
Fig. 27.1
Pedigree drawing of family PKRD320 illustrates segregation of variants identified in ZNF408 and C1QTNF4 with the retinal phenotype. Asterisk indicates the individuals that were chosen for whole-exome sequencing
Fig. 27.2
Fig. 27.2
Illustration of amino acid conservation of Arg435 in ZNF408 and Gly301 in C1QTNF4 in their respective orthologs
See this image and copyright information in PMC

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References

    1. Avila-Fernandez A, Perez-Carro R, Corton M et al. (2015) Whole-exome sequencing reveals ZNF408 as a new gene associated with autosomal recessive retinitis pigmentosa with vitreal alterations. Hum Mol Genet 24:4037–4048 - PubMed
    1. Ayyagari R, Kakuk LE, Bingham EL et al. (2000) Spectrum of color gene deletions and phenotype in patients with blue cone monochromacy. Hum Genet 107:75–82 - PubMed
    1. Ayyagari R, Mandal MN, Karoukis AJ et al. (2005) Late-onset macular degeneration and long anterior lens zonules result from a CTRP5 gene mutation. Invest Ophthalmol Vis Sci 46:3363–3371 - PubMed
    1. Boughman JA, Fishman GA (1983) A genetic analysis of retinitis pigmentosa. Br J Ophthalmol 67:449–454 - PMC - PubMed
    1. Boughman JA, Conneally PM, Nance WE (1980) Population genetic studies of retinitis pigmentosa. Am J Hum Genet 32:223–235 - PMC - PubMed

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