Detection of Cryptic Fragile X Full Mutation Alleles by Southern Blot in a Female and Her Foetal DNA via Chorionic Villus Sampling, Complicated by Mosaicism for 45,X0/46,XX/47,XXX
We describe a female with a 72 CGG <i>FMR1</i> premutation (PM) (CGG 55–199) and family history of fragile X syndrome (FXS), referred for prenatal testing. The proband had a high risk of having an affected pregnancy with a full mutation allele (FM) (CGG > 200), that causes FXS through...
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doaj-04c1d516107740548935745a478307dc2021-06-01T00:56:54ZengMDPI AGGenes2073-44252021-05-011279879810.3390/genes12060798Detection of Cryptic Fragile X Full Mutation Alleles by Southern Blot in a Female and Her Foetal DNA via Chorionic Villus Sampling, Complicated by Mosaicism for 45,X0/46,XX/47,XXXAlison Pandelache0David Francis1Ralph Oertel2Rebecca Dickson3Rani Sachdev4Ling Ling5Dinusha Gamage6David E. Godler7Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, VIC 3052, AustraliaVictorian Clinical Genetics Services, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, VIC 3052, AustraliaVictorian Clinical Genetics Services, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, VIC 3052, AustraliaMaternal Fetal Medicine Department, Royal Hospital for Women, Randwick, NSW 2031, AustraliaCentre for Clinical Genetics, Sydney Children’s Hospital, Randwick, NSW 2031, AustraliaDiagnosis and Development, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, VIC 3052, AustraliaDiagnosis and Development, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, VIC 3052, AustraliaDiagnosis and Development, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, VIC 3052, AustraliaWe describe a female with a 72 CGG <i>FMR1</i> premutation (PM) (CGG 55–199) and family history of fragile X syndrome (FXS), referred for prenatal testing. The proband had a high risk of having an affected pregnancy with a full mutation allele (FM) (CGG > 200), that causes FXS through hypermethylation of the <i>FMR1</i> promoter. The CGG sizing analysis in this study used AmplideX triplet repeat primed polymerase chain reaction (TP-PCR) and long-range methylation sensitive PCR (mPCR). These methods detected a 73 CGG PM allele in the proband’s blood, and a 164 CGG PM allele in her male cultured chorionic villus sample (CVS). In contrast, the Southern blot analysis showed mosaicism for: (i) a PM (71 CGG) and an FM (285–768 CGG) in the proband’s blood, and (ii) a PM (165 CGG) and an FM (408–625 CGG) in the male CVS. The <i>FMR1</i> methylation analysis, using an EpiTYPER system in the proband, showed levels in the range observed for mosaic Turner syndrome. This was confirmed by molecular and cytogenetic karyotyping, identifying 45,X0/46,XX/47,XXX lines. In conclusion, this case highlights the importance of Southern blot in pre- and postnatal testing for presence of an FM, which was not detected using AmplideX TP-PCR or mPCR in the proband and her CVS.https://www.mdpi.com/2073-4425/12/6/798fragileX syndromeFMR1mosaicismCGGcultured chorionic villus |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alison Pandelache David Francis Ralph Oertel Rebecca Dickson Rani Sachdev Ling Ling Dinusha Gamage David E. Godler |
spellingShingle |
Alison Pandelache David Francis Ralph Oertel Rebecca Dickson Rani Sachdev Ling Ling Dinusha Gamage David E. Godler Detection of Cryptic Fragile X Full Mutation Alleles by Southern Blot in a Female and Her Foetal DNA via Chorionic Villus Sampling, Complicated by Mosaicism for 45,X0/46,XX/47,XXX Genes fragile X syndrome FMR1 mosaicism CGG cultured chorionic villus |
author_facet |
Alison Pandelache David Francis Ralph Oertel Rebecca Dickson Rani Sachdev Ling Ling Dinusha Gamage David E. Godler |
author_sort |
Alison Pandelache |
title |
Detection of Cryptic Fragile X Full Mutation Alleles by Southern Blot in a Female and Her Foetal DNA via Chorionic Villus Sampling, Complicated by Mosaicism for 45,X0/46,XX/47,XXX |
title_short |
Detection of Cryptic Fragile X Full Mutation Alleles by Southern Blot in a Female and Her Foetal DNA via Chorionic Villus Sampling, Complicated by Mosaicism for 45,X0/46,XX/47,XXX |
title_full |
Detection of Cryptic Fragile X Full Mutation Alleles by Southern Blot in a Female and Her Foetal DNA via Chorionic Villus Sampling, Complicated by Mosaicism for 45,X0/46,XX/47,XXX |
title_fullStr |
Detection of Cryptic Fragile X Full Mutation Alleles by Southern Blot in a Female and Her Foetal DNA via Chorionic Villus Sampling, Complicated by Mosaicism for 45,X0/46,XX/47,XXX |
title_full_unstemmed |
Detection of Cryptic Fragile X Full Mutation Alleles by Southern Blot in a Female and Her Foetal DNA via Chorionic Villus Sampling, Complicated by Mosaicism for 45,X0/46,XX/47,XXX |
title_sort |
detection of cryptic fragile x full mutation alleles by southern blot in a female and her foetal dna via chorionic villus sampling, complicated by mosaicism for 45,x0/46,xx/47,xxx |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2021-05-01 |
description |
We describe a female with a 72 CGG <i>FMR1</i> premutation (PM) (CGG 55–199) and family history of fragile X syndrome (FXS), referred for prenatal testing. The proband had a high risk of having an affected pregnancy with a full mutation allele (FM) (CGG > 200), that causes FXS through hypermethylation of the <i>FMR1</i> promoter. The CGG sizing analysis in this study used AmplideX triplet repeat primed polymerase chain reaction (TP-PCR) and long-range methylation sensitive PCR (mPCR). These methods detected a 73 CGG PM allele in the proband’s blood, and a 164 CGG PM allele in her male cultured chorionic villus sample (CVS). In contrast, the Southern blot analysis showed mosaicism for: (i) a PM (71 CGG) and an FM (285–768 CGG) in the proband’s blood, and (ii) a PM (165 CGG) and an FM (408–625 CGG) in the male CVS. The <i>FMR1</i> methylation analysis, using an EpiTYPER system in the proband, showed levels in the range observed for mosaic Turner syndrome. This was confirmed by molecular and cytogenetic karyotyping, identifying 45,X0/46,XX/47,XXX lines. In conclusion, this case highlights the importance of Southern blot in pre- and postnatal testing for presence of an FM, which was not detected using AmplideX TP-PCR or mPCR in the proband and her CVS. |
topic |
fragile X syndrome FMR1 mosaicism CGG cultured chorionic villus |
url |
https://www.mdpi.com/2073-4425/12/6/798 |
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