OGM and WES identifies translocation breakpoints in PKD1 gene in an polycystic kidney patient and healthy baby delivered using PGT.
ADPKD
Karyotype analysis
PGT
PKD1
Reciprocal translocations
WES
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
13 11 2023
13 11 2023
Historique:
received:
10
06
2023
accepted:
02
11
2023
medline:
14
11
2023
pubmed:
13
11
2023
entrez:
12
11
2023
Statut:
epublish
Résumé
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common autosomal dominant genetic diseases. Whole exome sequencing (WES) is a routine tool for diagnostic confirmation of genetic diseases, and it is usually performed to confirm the clinical diagnosis in ADPKD. Reciprocal translocation is the most common chromosomal structural abnormalities and most of its carriers have normal phenotypes until they are encountered infertility problems in adulthood. However, for the polycystic kidney disease caused by abnormal chromosome structure, WES is difficult to achieve the purpose of gene diagnosis. ADPKD-related genes were detected by WES; Chromosomal karyotyping and Optical Genome Mapping (OGM) were used to detect structural variant; The genomic break-point locations and the abnormal splicing were detected by reverse transcription-PCR and Sanger sequencing; The karyomapping gene chip and Next-Generation Sequencing (NGS) were performed to screen aneuploidy and to distinguish the non-carrier embryos from the carrier embryos. No pathogenic variant was found after the first round of WES analysis. Karyotyping data showed 46, XX, t (16; 17) (p13.3; q21.3). With the help of OGM, the translocation breakpoint on chromosome 16 was located within the PKD1 gene. With re-analysis of WES raw data, the breakpoint of translocation was verified to be located at the c.10618 + 3 of PKD1 gene. Based on this molecular diagnosis, a non-carrier embryo was selected out from three blastocysts. With preimplantation genetic testing (PGT) after in vitro fertilization (IVF), it was then transferred into uterus. With confirmation by prenatal and postnatal testing, the pedigree delivered a healthy baby. We identified a case of ADPKD caused by balanced translocation and assisted the patient to have a healthy child. When the phenotype was closely related with a monogenic disease and the WES analysis was negative, chromosomal structural analysis would be recommended for further genetic diagnosis. Based on the precision diagnosis, preventing the recurrence of hereditary diseases in offspring would be reachable.
Sections du résumé
BACKGROUND
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common autosomal dominant genetic diseases. Whole exome sequencing (WES) is a routine tool for diagnostic confirmation of genetic diseases, and it is usually performed to confirm the clinical diagnosis in ADPKD. Reciprocal translocation is the most common chromosomal structural abnormalities and most of its carriers have normal phenotypes until they are encountered infertility problems in adulthood. However, for the polycystic kidney disease caused by abnormal chromosome structure, WES is difficult to achieve the purpose of gene diagnosis.
METHODS
ADPKD-related genes were detected by WES; Chromosomal karyotyping and Optical Genome Mapping (OGM) were used to detect structural variant; The genomic break-point locations and the abnormal splicing were detected by reverse transcription-PCR and Sanger sequencing; The karyomapping gene chip and Next-Generation Sequencing (NGS) were performed to screen aneuploidy and to distinguish the non-carrier embryos from the carrier embryos.
RESULTS
No pathogenic variant was found after the first round of WES analysis. Karyotyping data showed 46, XX, t (16; 17) (p13.3; q21.3). With the help of OGM, the translocation breakpoint on chromosome 16 was located within the PKD1 gene. With re-analysis of WES raw data, the breakpoint of translocation was verified to be located at the c.10618 + 3 of PKD1 gene. Based on this molecular diagnosis, a non-carrier embryo was selected out from three blastocysts. With preimplantation genetic testing (PGT) after in vitro fertilization (IVF), it was then transferred into uterus. With confirmation by prenatal and postnatal testing, the pedigree delivered a healthy baby.
CONCLUSION
We identified a case of ADPKD caused by balanced translocation and assisted the patient to have a healthy child. When the phenotype was closely related with a monogenic disease and the WES analysis was negative, chromosomal structural analysis would be recommended for further genetic diagnosis. Based on the precision diagnosis, preventing the recurrence of hereditary diseases in offspring would be reachable.
Identifiants
pubmed: 37953234
doi: 10.1186/s12920-023-01725-2
pii: 10.1186/s12920-023-01725-2
pmc: PMC10642002
doi:
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
285Informations de copyright
© 2023. The Author(s).
Références
J Assist Reprod Genet. 2020 Aug;37(8):2025-2031
pubmed: 32500460
BMC Genet. 2016 May 04;17(1):64
pubmed: 27142071
J Genet Genomics. 2020 Nov 20;47(11):718-721
pubmed: 33775291
J Am Soc Nephrol. 2018 Oct;29(10):2593-2600
pubmed: 30135240
Am J Hum Genet. 2021 Aug 5;108(8):1409-1422
pubmed: 34237280
Bioinformatics. 2013 Jan 1;29(1):124-5
pubmed: 23104884
Genet Med. 2020 Aug;22(8):1374-1383
pubmed: 32398770
Clin Transl Med. 2021 Jul;11(7):e490
pubmed: 34323405
Nephrol Dial Transplant. 2017 Aug 01;32(8):1356-1363
pubmed: 27325254
Front Genet. 2022 Jan 18;12:810900
pubmed: 35116057
Transl Res. 2016 Nov;177:31-40.e6
pubmed: 27370899
Genes (Basel). 2021 Nov 21;12(11):
pubmed: 34828442
Hum Fertil (Camb). 2001;4(3):168-71
pubmed: 11591275
Am J Hum Genet. 1991 Nov;49(5):995-1013
pubmed: 1928105
Eur J Hum Genet. 2022 Nov;30(11):1239-1243
pubmed: 35879407
Bioinformatics. 2010 Mar 1;26(5):589-95
pubmed: 20080505
Eur J Hum Genet. 2002 Dec;10(12):801-6
pubmed: 12461686
J Assist Reprod Genet. 2020 Mar;37(3):509-516
pubmed: 32026199
Eur J Med Genet. 2021 Apr;64(4):104183
pubmed: 33639313
Hereditas. 2018 Sep 28;155:32
pubmed: 30279644
J Am Soc Nephrol. 2018 Jan;29(1):13-23
pubmed: 29038287
Hum Mutat. 2012 Aug;33(8):1239-50
pubmed: 22508176
Hum Genet. 2009 Jul;126(1):133-47
pubmed: 19347365
Eur J Hum Genet. 2005 Jan;13(1):6-25
pubmed: 15523501
Genome Res. 2017 May;27(5):778-786
pubmed: 28159771