TY - CHAP
T1 - Whole-exome sequencing identifies novel variants that co-segregates with autosomal recessive retinal degeneration in a Pakistani pedigree
AU - Biswas, Pooja
AU - Naeem, Muhammad Asif
AU - Ali, Muhammad Hassaan
AU - Assir, Muhammad Zaman
AU - Khan, Shaheen N.
AU - Riazuddin, Sheikh
AU - Hejtmancik, J. Fielding
AU - Riazuddin, S. Amer
AU - Ayyagari, Radha
N1 - Funding Information:
This work was supported by NIH-EY021237, NIH-EY002162, NIH-EY0020846, NIH-P30EY022589, Foundation Fighting Blindness (RA), and Research to Prevent Blindness (RA).
Funding Information:
Dr. Ayyagari, the principal investigator and corresponding author had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Support: This work was supported by NEI-NIH grants EY014375, NIH-R01EY021237, NIH-R01EY013198, Foundation Fighting Blindness, and Research to Prevent Blindness.
Publisher Copyright:
© 2018, Springer International Publishing AG, part of Springer Nature.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - C1QTNF4
KW - Novel variants
KW - Retinal degeneration
KW - Whole-exome sequencing
KW - ZNF408
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U2 - 10.1007/978-3-319-75402-4_27
DO - 10.1007/978-3-319-75402-4_27
M3 - Chapter
C2 - 29721947
AN - SCOPUS:85046689855
T3 - Advances in Experimental Medicine and Biology
SP - 219
EP - 228
BT - Advances in Experimental Medicine and Biology
PB - Springer New York LLC
ER -