Preimplantation genetic testing for a chr14q32 microdeletion in a family with Kagami-Ogata syndrome and Temple syndrome
Por:
Sabria-Bach J, Monteagudo-Sánchez A, Sánchez-Delgado M, Ferguson-Smith AC, Gómez O, Pertierra-Cortada A, Tenorio J, Nevado J, Lapunzina P, Pereda Aguirre A, Giménez Sevilla C, Toro Toro E, Perez de Nanclares G and Monk D
Publicada:
1 mar 2022
Ahead of Print:
1 feb 2021
Resumen:
Introduction Kagami-Ogata syndrome (KOS14) and Temple syndrome (TS14) are two disorders associated with reciprocal alterations within the chr14q32 imprinted domain. Here, we present a work-up strategy for preimplantation genetic testing (PGT) to avoid the transmission of a causative micro-deletion. Methods We analysed DNA from the KOS14 index case and parents using methylation-sensitive ligation-mediated probe amplification and methylation pyrosequencing. The extent of the deletion was mapped using SNP arrays. PGT was performed in trophectoderm samples in order to identify unaffected embryos. Samples were amplified using multiple displacement amplification, followed by genome-wide SNP genotyping to determine the at-risk haplotype and next-generation sequencing to determine aneuploidies. Results A fully methylated pattern at the normally paternally methylated IG-DMR and MEG3 DMR in the KOS14 proband, accompanied by an unmethylated profile in the TS14 mother was consistent with maternal and paternal transmission of a deletion, respectively. Further analysis revealed a 108 kb deletion in both cases. The inheritance of the deletion on different parental alleles was consistent with the opposing phenotypes. In vitro fertilisation with intracytoplasmatic sperm injection and PGT were used to screen for deletion status and to transfer an unaffected embryo in this couple. A single euploid-unaffected embryo was identified resulting in a healthy baby born. Discussion We identify a microdeletion responsible for multigeneration KOS14 and TS14 within a single family where carriers have a 50% risk of transmitting the deletion to their offspring. We show that PGT can successfully be offered to couples with IDs caused by genetic anomalies.
Filiaciones:
Sabria-Bach J:
BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Sant Joan de Déu and Hospital Clinic, Barcelona, Spain
Monteagudo-Sánchez A:
Cancer Epigenetics and Biology Program, Bellvitge Institute for Biomedical Research, Barcelona, Spain
Sánchez-Delgado M:
Cancer Epigenetics and Biology Program, Bellvitge Institute for Biomedical Research, Barcelona, Spain
Ferguson-Smith AC:
Department of Genetics, University of Cambridge, Cambridge, Cambridgeshire, UK
Gómez O:
BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Sant Joan de Déu and Hospital Clinic, Barcelona, Spain
Pertierra-Cortada A:
BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Sant Joan de Déu and Hospital Clinic, Barcelona, Spain
Tenorio J:
INGEMM (Instituto de Genética Médica y Molecular), Hospital Universitario La Paz-IdiPaz, Hospital universitario la Paz, Madrid, Spain
CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Madrid, Spain
ITHACA, European Reference Network on Rare Congenital Malformations and Rare Intellectual Disabilities, Madrid, Spain
Nevado J:
INGEMM (Instituto de Genética Médica y Molecular), Hospital Universitario La Paz-IdiPaz, Hospital universitario la Paz, Madrid, Spain
CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Madrid, Spain
ITHACA, European Reference Network on Rare Congenital Malformations and Rare Intellectual Disabilities, Madrid, Spain
Lapunzina P:
INGEMM (Instituto de Genética Médica y Molecular), Hospital Universitario La Paz-IdiPaz, Hospital universitario la Paz, Madrid, Spain
CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Madrid, Spain
ITHACA, European Reference Network on Rare Congenital Malformations and Rare Intellectual Disabilities, Madrid, Spain
Pereda Aguirre A:
Molecular (Epi)Genetics Laboratory, Bioaraba Health Research Institute, Vitoria-Gasteiz, Spain
Giménez Sevilla C:
Reprogenetics, Barcelona, Spain
Toro Toro E:
Reprogenetics, Barcelona, Spain
Perez de Nanclares G:
Molecular (Epi)Genetics Laboratory, Bioaraba Health Research Institute, Vitoria-Gasteiz, Spain
Monk D:
Biomedical Research Center, School of Biological Sciences, University of East Anglia, Norwich, UK
Green Accepted
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