title: Molecular characterization of 39 de novo sSMC: contribution to prognosis and genetic counselling, a prospective study.
abstract: Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that cannot be characterized by karyotype. In many prenatal cases of de novo sSMC, the outcome of pregnancy is difficult to predict because the euchromatin content is unclear. This study aimed to determine the presence or absence of euchromatin material of 39 de novo prenatally ascertained sSMC by array-comparative genomic hybridization (array-CGH) or single nucleotide polymorphism (SNP) array. Cases were prospectively ascertained from the study of 65,000 prenatal samples [0.060%; 95% confidence interval (CI), 0.042-0.082]. Array-CGH showed that 22 markers were derived from non-acrocentric markers (56.4%) and 7 from acrocentic markers (18%). The 10 additional cases remained unidentified (25.6%), but 7 of 10 could be further identified using fluorescence in situ hybridization; 69% of de novo sSMC contained euchromatin material, 95.4% of which for non-acrocentric markers. Some sSMC containing euchromatin had a normal phenotype (31% for non-acrocentric and 75% for acrocentric markers). Statistical differences between normal and abnormal phenotypes were shown for the size of the euchromatin material (more or less than 1 Mb, p = 0.0006) and number of genes (more or less than 10, p = 0.0009). This study is the largest to date and shows the utility of array-CGH or SNP array in the detection and characterization of de novo sSMC in a prenatal context.
authors.affiliation: Département de Génétique, Hôpital Le Bocage, Université de Bourgogne, Dijon, France.
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authors.lastname: Marle
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authors.lastname: Aboura
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authors.lastname: Joly-Helas
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authors.lastname: Quilichini
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authors.lastname: Simon-Bouy
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authors.lastname: Becker
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authors.lastname: Stora
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authors.initials: S
authors.lastname: Amblard
authors.forename: M
authors.initials: M
authors.lastname: Doco-Fenzy
authors.forename: D
authors.initials: D
authors.lastname: Molina Gomes
authors.forename: F
authors.initials: F
authors.lastname: Girard-Lemaire
authors.forename: M P
authors.initials: MP
authors.lastname: Cordier
authors.forename: V
authors.initials: V
authors.lastname: Satre
authors.forename: A
authors.initials: A
authors.lastname: Schneider
authors.forename: N
authors.initials: N
authors.lastname: Lemeur
authors.forename: P
authors.initials: P
authors.lastname: Chambon
authors.forename: S
authors.initials: S
authors.lastname: Jacquemont
authors.forename: F
authors.initials: F
authors.lastname: Fellmann
authors.forename: A
authors.initials: A
authors.lastname: Vigouroux-Castera
authors.forename: R
authors.initials: R
authors.lastname: Molignier
authors.forename: A
authors.initials: A
authors.lastname: Delaye
authors.forename: E
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authors.lastname: Pipiras
authors.forename: A
authors.initials: A
authors.lastname: Liquier
authors.forename: T
authors.initials: T
authors.lastname: Rousseau
authors.forename: A L
authors.initials: AL
authors.lastname: Mosca
authors.forename: V
authors.initials: V
authors.lastname: Kremer
authors.forename: M
authors.initials: M
authors.lastname: Payet
authors.forename: C
authors.initials: C
authors.lastname: Rangon
authors.forename: F
authors.initials: F
authors.lastname: Mugneret
authors.forename: S
authors.initials: S
authors.lastname: Aho
authors.forename: L
authors.initials: L
authors.lastname: Faivre
authors.forename: P
authors.initials: P
authors.lastname: Callier
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D005260:Female; D005602:France; D056726:Genetic Association Studies; D005817:Genetic Counseling; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011379:Prognosis; D011446:Prospective Studies; D012306:Risk; D013557:Switzerland; D055815:Young Adult
chemical_list: D005819:Genetic Markers
keywords: array-CGH; de novo sSMC; genotype-phenotype correlation; prenatal diagnosis; small supernumerary chromosome marker