TY - JOUR
T1 - Analysis of an NGS retinopathy panel detects chromosome 1 uniparental isodisomy in a patient with RPE65-related leber congenital amaurosis
AU - Motta, Fabiana Louise
AU - Filippelli-Silva, Rafael
AU - Kitajima, Joao Paulo
AU - Batista, Denise A.
AU - Wohler, Elizabeth S.
AU - Sobreira, Nara L.
AU - Martin, Renan Paulo
AU - Ferraz Sallum, Juliana Maria
N1 - Funding Information:
The authors thank the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES - Financing Code 001) (FLM), and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP - 2014/20965-3) (RPM) for fellowship support.
Funding Information:
The authors thank the Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - Brasil (CAPES - Financing Code 001) (FLM), and Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo (FAPESP - 2014/20965-3) (RPM) for fellowship support.
Publisher Copyright:
© 2021 Taylor & Francis Group, LLC.
PY - 2021
Y1 - 2021
N2 - Purpose: This study aims to demonstrate the possibility of detecting segmental uniparental isodisomy (iUPD) using a next-generation sequencing gene panel by reporting a Leber congenital amaurosis (LCA) case caused by a homozygous pathogenic variant in RPE65 (c.1022 T > C:p.Leu341Ser) inherited exclusively from the proband’s mother. Methods: Samples from the trio (proband, mother, and father) were sequenced with a next-generation sequencing (NGS) retinopathy gene panel (224 genes) and the VCF file containing all variants was used in order to determine single nucleotide variant (SNV) counts from each sample across all chromosomes. Results: Trio analysis showed that of 81 Chr1 inherited variants 41 were exclusively maternal, including 21 homozygous. The other 40 variants were common to both parents. On remaining autosomal chromosomes (Chr2-22) 645 inherited variants were found, 147 of them were exclusively maternal and 132 exclusively paternal. Based on these NGS data, it was possible to note that the proband’s chromosomes 1 are more similar to his mother’s chromosome 1 than his father’s, suggesting the pathogenic homozygous variant found in this patient was inherited exclusively from the mother due to uniparental maternal isodisomy. Conclusions: This study presents a secondary analysis pipeline to identify responsible variants for a phenotype and the correct inheritance pattern, which is a critical step to the proper and accurate genetic counseling of all family members. In addition, this approach could be used to determine iUPD in different Mendelian disorders if the sequencing panel identifies variants spread throughout the genome.
AB - Purpose: This study aims to demonstrate the possibility of detecting segmental uniparental isodisomy (iUPD) using a next-generation sequencing gene panel by reporting a Leber congenital amaurosis (LCA) case caused by a homozygous pathogenic variant in RPE65 (c.1022 T > C:p.Leu341Ser) inherited exclusively from the proband’s mother. Methods: Samples from the trio (proband, mother, and father) were sequenced with a next-generation sequencing (NGS) retinopathy gene panel (224 genes) and the VCF file containing all variants was used in order to determine single nucleotide variant (SNV) counts from each sample across all chromosomes. Results: Trio analysis showed that of 81 Chr1 inherited variants 41 were exclusively maternal, including 21 homozygous. The other 40 variants were common to both parents. On remaining autosomal chromosomes (Chr2-22) 645 inherited variants were found, 147 of them were exclusively maternal and 132 exclusively paternal. Based on these NGS data, it was possible to note that the proband’s chromosomes 1 are more similar to his mother’s chromosome 1 than his father’s, suggesting the pathogenic homozygous variant found in this patient was inherited exclusively from the mother due to uniparental maternal isodisomy. Conclusions: This study presents a secondary analysis pipeline to identify responsible variants for a phenotype and the correct inheritance pattern, which is a critical step to the proper and accurate genetic counseling of all family members. In addition, this approach could be used to determine iUPD in different Mendelian disorders if the sequencing panel identifies variants spread throughout the genome.
KW - RPE65 gene
KW - Uniparental isodisomy
KW - diagnosis
KW - gene panel
KW - next-generation sequencing
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U2 - 10.1080/13816810.2021.1938136
DO - 10.1080/13816810.2021.1938136
M3 - Article
C2 - 34157943
AN - SCOPUS:85108632908
SN - 1381-6810
VL - 42
SP - 553
EP - 560
JO - Ophthalmic genetics
JF - Ophthalmic genetics
IS - 5
ER -