Prenatal diagnosis of fragile x syndrome: (cgg)n expansion and methylation of chorionic villus samples

Sergi Castellví‐Bel, Montserrat Milà, Anna Soler, Ana Carrió, Aurora Sánchez, Margarita Villa, M. Dolores Jiménez, Xavier P. Estivill

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Fragile X syndrome is the most common form of inherited mental retardation, due to an expansion of the (CGG)n trinucleotide repeat in the FMR‐1 gene and hypermethylation of its 5′ upstream CpG island. Two major problems remain to be resolved for fragile X prenatal diagnosis: the abnormal methylation patterns of chorionic villus samples (CVS) and the inability to predict the mental status of females with the full mutation. We present here the results of ten prenatal diagnoses of fragile X syndrome using Southern blotting and polymerase chain reaction (PCR) amplification, and the analysis of 50 further CVS to test the methylation status of the CpG island of the FMR‐1 gene. In the ten ‘at‐risk’ CVS, eight normal (five males and three females) and two affected male fetuses were detected. Absence of methylation in the CVS was observed in two cases, which was not found upon subsequent examination of the newborn or of fetal tissues. In the 50 CVS not ‘at risk’ for fragile X syndrome, abnormal fragment patterns for probe StB12.3 were detected in 32 per cent for female and 24 per cent for male fetuses. This abnormal pattern could be due to absent or partial methylation of the CpG island of the FMR‐1 gene in chorionic villus tissues.

Original languageEnglish
Pages (from-to)801-807
Number of pages7
JournalPrenatal Diagnosis
Volume15
Issue number9
DOIs
Publication statusPublished - 1995
Externally publishedYes

Fingerprint

Chorionic Villi
Prenatal Diagnosis
Methylation
Fragile X Syndrome
CpG Islands
Fetus
Genes
Trinucleotide Repeats
Southern Blotting
Intellectual Disability
Polymerase Chain Reaction
Mutation

Keywords

  • chorionic villus samples
  • DNA methylation
  • FMR‐1 gene
  • fragile X syndrome
  • prenatal diagnosis

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Genetics(clinical)

Cite this

Prenatal diagnosis of fragile x syndrome : (cgg)n expansion and methylation of chorionic villus samples. / Castellví‐Bel, Sergi; Milà, Montserrat; Soler, Anna; Carrió, Ana; Sánchez, Aurora; Villa, Margarita; Jiménez, M. Dolores; Estivill, Xavier P.

In: Prenatal Diagnosis, Vol. 15, No. 9, 1995, p. 801-807.

Research output: Contribution to journalArticle

Castellví‐Bel, S, Milà, M, Soler, A, Carrió, A, Sánchez, A, Villa, M, Jiménez, MD & Estivill, XP 1995, 'Prenatal diagnosis of fragile x syndrome: (cgg)n expansion and methylation of chorionic villus samples', Prenatal Diagnosis, vol. 15, no. 9, pp. 801-807. https://doi.org/10.1002/pd.1970150903
Castellví‐Bel, Sergi ; Milà, Montserrat ; Soler, Anna ; Carrió, Ana ; Sánchez, Aurora ; Villa, Margarita ; Jiménez, M. Dolores ; Estivill, Xavier P. / Prenatal diagnosis of fragile x syndrome : (cgg)n expansion and methylation of chorionic villus samples. In: Prenatal Diagnosis. 1995 ; Vol. 15, No. 9. pp. 801-807.
@article{e59bfc97ae6b4d92b769233573047e98,
title = "Prenatal diagnosis of fragile x syndrome: (cgg)n expansion and methylation of chorionic villus samples",
abstract = "Fragile X syndrome is the most common form of inherited mental retardation, due to an expansion of the (CGG)n trinucleotide repeat in the FMR‐1 gene and hypermethylation of its 5′ upstream CpG island. Two major problems remain to be resolved for fragile X prenatal diagnosis: the abnormal methylation patterns of chorionic villus samples (CVS) and the inability to predict the mental status of females with the full mutation. We present here the results of ten prenatal diagnoses of fragile X syndrome using Southern blotting and polymerase chain reaction (PCR) amplification, and the analysis of 50 further CVS to test the methylation status of the CpG island of the FMR‐1 gene. In the ten ‘at‐risk’ CVS, eight normal (five males and three females) and two affected male fetuses were detected. Absence of methylation in the CVS was observed in two cases, which was not found upon subsequent examination of the newborn or of fetal tissues. In the 50 CVS not ‘at risk’ for fragile X syndrome, abnormal fragment patterns for probe StB12.3 were detected in 32 per cent for female and 24 per cent for male fetuses. This abnormal pattern could be due to absent or partial methylation of the CpG island of the FMR‐1 gene in chorionic villus tissues.",
keywords = "chorionic villus samples, DNA methylation, FMR‐1 gene, fragile X syndrome, prenatal diagnosis",
author = "Sergi Castellv{\'i}‐Bel and Montserrat Mil{\`a} and Anna Soler and Ana Carri{\'o} and Aurora S{\'a}nchez and Margarita Villa and Jim{\'e}nez, {M. Dolores} and Estivill, {Xavier P.}",
year = "1995",
doi = "10.1002/pd.1970150903",
language = "English",
volume = "15",
pages = "801--807",
journal = "Prenatal Diagnosis",
issn = "0197-3851",
publisher = "John Wiley and Sons Ltd",
number = "9",

}

TY - JOUR

T1 - Prenatal diagnosis of fragile x syndrome

T2 - (cgg)n expansion and methylation of chorionic villus samples

AU - Castellví‐Bel, Sergi

AU - Milà, Montserrat

AU - Soler, Anna

AU - Carrió, Ana

AU - Sánchez, Aurora

AU - Villa, Margarita

AU - Jiménez, M. Dolores

AU - Estivill, Xavier P.

PY - 1995

Y1 - 1995

N2 - Fragile X syndrome is the most common form of inherited mental retardation, due to an expansion of the (CGG)n trinucleotide repeat in the FMR‐1 gene and hypermethylation of its 5′ upstream CpG island. Two major problems remain to be resolved for fragile X prenatal diagnosis: the abnormal methylation patterns of chorionic villus samples (CVS) and the inability to predict the mental status of females with the full mutation. We present here the results of ten prenatal diagnoses of fragile X syndrome using Southern blotting and polymerase chain reaction (PCR) amplification, and the analysis of 50 further CVS to test the methylation status of the CpG island of the FMR‐1 gene. In the ten ‘at‐risk’ CVS, eight normal (five males and three females) and two affected male fetuses were detected. Absence of methylation in the CVS was observed in two cases, which was not found upon subsequent examination of the newborn or of fetal tissues. In the 50 CVS not ‘at risk’ for fragile X syndrome, abnormal fragment patterns for probe StB12.3 were detected in 32 per cent for female and 24 per cent for male fetuses. This abnormal pattern could be due to absent or partial methylation of the CpG island of the FMR‐1 gene in chorionic villus tissues.

AB - Fragile X syndrome is the most common form of inherited mental retardation, due to an expansion of the (CGG)n trinucleotide repeat in the FMR‐1 gene and hypermethylation of its 5′ upstream CpG island. Two major problems remain to be resolved for fragile X prenatal diagnosis: the abnormal methylation patterns of chorionic villus samples (CVS) and the inability to predict the mental status of females with the full mutation. We present here the results of ten prenatal diagnoses of fragile X syndrome using Southern blotting and polymerase chain reaction (PCR) amplification, and the analysis of 50 further CVS to test the methylation status of the CpG island of the FMR‐1 gene. In the ten ‘at‐risk’ CVS, eight normal (five males and three females) and two affected male fetuses were detected. Absence of methylation in the CVS was observed in two cases, which was not found upon subsequent examination of the newborn or of fetal tissues. In the 50 CVS not ‘at risk’ for fragile X syndrome, abnormal fragment patterns for probe StB12.3 were detected in 32 per cent for female and 24 per cent for male fetuses. This abnormal pattern could be due to absent or partial methylation of the CpG island of the FMR‐1 gene in chorionic villus tissues.

KW - chorionic villus samples

KW - DNA methylation

KW - FMR‐1 gene

KW - fragile X syndrome

KW - prenatal diagnosis

UR - http://www.scopus.com/inward/record.url?scp=0029098429&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029098429&partnerID=8YFLogxK

U2 - 10.1002/pd.1970150903

DO - 10.1002/pd.1970150903

M3 - Article

C2 - 8559749

AN - SCOPUS:0029098429

VL - 15

SP - 801

EP - 807

JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

SN - 0197-3851

IS - 9

ER -