An unusual familial chromosome 9 “variant” with variable phenotype: characterization by CGH analysis

Goumy, Carole; M, Mihaescu; Tchirkov, Andréï; Giollant, M.; Bonnet-Dupeyron, Marie-Noëlle; Jaffray, J.Y.; Geneix, A; Perissel, B; Francannet, Christine; Boespflug‐Tanguy, Odile; Vago, Philippe

doi:10.1016/s1286-0115(05)83241-2

Cited by 7 publications

(4 citation statements)

References 37 publications

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“…Comparative genomic hybridization (CGH) was performed on chromosome spreads using DNA extracted from cultured amniocytes, as previously described [du Manoir et al, 1995; Goumy et al, 2005], with a resolution of 3–5 Mb determined in our laboratory. The CGH confirmed the 11q deletion and mapped the breakpoints at 11q14.3 and 11q22.1 (Fig.…”

Section: Clinical Report and Cytogenetic Studymentioning

confidence: 99%

Familial deletion 11q14.3–q22.1 without apparent phenotypic consequences: A haplosufficient 8.5 Mb region

Goumy

Gouas

Tchirkov

et al. 2008

American J of Med Genetics Pt A

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We present the prenatal diagnosis of a chromosome 11q14.3-q22.1 deletion identified in three generations without apparent phenotypic consequences. A 25-year-old G2, P1 woman underwent amniocentesis at 15 weeks' gestation because of a positive result for Down syndrome maternal serum-screening test (1/70). The fetal karyotype revealed an interstitial deletion of the long arm of chromosome 11 confirmed by CGH and FISH: 46,XX,del(11)(q14.3q22.1). The mother and grandfather of the fetus presented the same interstitial deletion with a little if any phenotype effect. The pregnancy was carried to term and resulted in the birth of a normal girl. To our knowledge, only one case of a chromosome 11q14.3-q21 deletion without phenotypic anomalies has been reported. Our study allows the initially described haplosufficient region to be extended from 3.6 Mb to at least 8.5 Mb. This large deletion was compatible with fertility and apparently normal phenotype. Identification of such chromosomal regions is important for prenatal diagnosis and genetic counseling.

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Section: Clinical Report and Cytogenetic Studymentioning

confidence: 99%

Familial deletion 11q14.3–q22.1 without apparent phenotypic consequences: A haplosufficient 8.5 Mb region

Goumy

Gouas

Tchirkov

et al. 2008

American J of Med Genetics Pt A

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“…To our knowledge, the presence of euchromatin in a pseudo-dicentric variant has only been demonstrated once before using metaphase CGH in an analogous dicentric duplication variant of 9p12 to q21 [Goumy et al, 2005]. A C-negative-band involving alpha satellite DNA in the qh region of chromosome 16 was previously described by Jalal et al [1993], but their variant was inverted and no euchromatic component was recorded.…”

Section: Discussionmentioning

confidence: 90%

“…3 ), (5) the euchromatic region overlaps multiple large CNVs in the Database of Genomic Variants (http://projects.tcag.ca/variation/) ( fig. 3 ), (6) heterochromatic variation does not normally have any phenotypic effect, (7) a heterochromatic position effect seems unlikely [Barber et al, 2006], and (8) analogous pseudo-dicentric variants of chromosome 9 have also been found in the normal sister [Lukusa et al, 2000], father, and grandparent of children ascertained with phenotypic abnormalities [Goumy et al, 2005]. It is therefore important to distinguish this EV from the pathogenic duplications of proximal 16q in which segments from bands 16q12.1 to 16q13 are found within the heterochromatic block of chromosome 16 and are associated with developmental delay, speech delay, learning difficulties, and behavioral problems ( fig.…”

Section: Discussionmentioning

confidence: 99%

A Novel Pseudo-Dicentric Variant of 16p11.2–q11.2 Contains Euchromatin from 16p11.2–p11.1 and Resembles Pathogenic Duplications of Proximal 16q

Barber

Brasch‐Andersen²,

Maloney³

et al. 2012

Cytogenet Genome Res

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An unusually large G-light band between 2 G-dark bands in the proximal long arm of chromosome 16 was found in a boy of 5 years of age ascertained with growth retardation, microcephaly, and dysmorphic features. Dual color bacterial artificial chromosome fluorescence in situ hybridization (BAC FISH) and oligonucleotide array comparative genomic hybridization (oaCGH) were used to show that these bands contained a euchromatic duplication of a minimum of 940 kb between base pairs 34,197,413–35,137,025 in 16p11.2–p11.1 as well as a duplication of the centromere and major 16qh/16p11.2 heterochromatic block, covering a minimum of 12.3 Mb. The same pseudo-dicentric chromosome was found in the father who has attention deficit hyperactivity disorder (ADHD). The euchromatic region is not known to be subject to imprinting and overlaps multiple large copy number variations (CNVs) in the Database of Genomic Variants as well as similar CNVs that are benign or of uncertain significance in the International Standards for Cytogenomic Arrays database. We conclude that this family has a novel pseudo-dicentric euchromatic variant of chromosome 16 that is unlikely to be the cause of the variable phenotype in father and son but needs to be distinguished from heterochromatic variants or pathogenic duplications of proximal 16q.

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“…Rather than extending into the gene rich, unique-sequence regions of distal 9q21, it seems more likely that the classical EVs of 9q13-q22 also contain SD cassette amplifications and that the pseudodicentric duplication variant of 9p12-q21 described by Goumy et al [2005] is restricted to the pericentromeric SD region. A total of 7-12 copies of a ∼ 1-Mb amplicon was found in the apparent duplication variants of 9p12 by Lecce et al [2006].…”

Section: Discussionmentioning

confidence: 99%

Another Family with a Euchromatic Duplication Variant of 9q13-q21.1 Derived from Segmentally Duplicated Pericentromeric Euchromatin

Barber

Rodrigues²,

Maloney

et al. 2013

Cytogenet Genome Res

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Microscopically visible copy number variations within the proximal short arm heterochromatin and proximal long arm of chromosome 9 have been described as euchromatic variants (EVs) and are derived from extensive segmental duplications (SDs) that map to both the proximal short and long arms of chromosome 9. Recently, 3-4 additional copies of an SD cassette were found in 2 families with duplication EVs of 9q13-q21. Here, we report a third family with a duplication EV of 9q13-q21.1 that was ascertained at prenatal diagnosis for advanced maternal age and found in the fetus and her phenotypically normal mother. Dual-colour fluorescence in situ hybridization with bacterial artificial chromosomes RP11-246P17 and RP11-211E19 was consistent with the EV chromosome having 1-2 additional copies of a similar SD cassette, except that the SD-boundary clone RP11-88I18 was not apparently included. It is important to distinguish the 9q13-q21.1 EVs from possible pathogenic imbalances of chromosome 9, especially at prenatal diagnosis, as these EVs have no established phenotypic or reproductive consequences. The nature of the G-dark bands in 9q13-q21 EVs is briefly discussed.

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An unusual familial chromosome 9 “variant” with variable phenotype: characterization by CGH analysis

Cited by 7 publications

References 37 publications

Familial deletion 11q14.3–q22.1 without apparent phenotypic consequences: A haplosufficient 8.5 Mb region

Familial deletion 11q14.3–q22.1 without apparent phenotypic consequences: A haplosufficient 8.5 Mb region

A Novel Pseudo-Dicentric Variant of 16p11.2–q11.2 Contains Euchromatin from 16p11.2–p11.1 and Resembles Pathogenic Duplications of Proximal 16q

Another Family with a Euchromatic Duplication Variant of 9q13-q21.1 Derived from Segmentally Duplicated Pericentromeric Euchromatin

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