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

Barber, John; Rodrigues, Renata; Maloney, Viv; Taborda, F.; Rodrigues, M. do C.; Bateman, Mark S.

doi:10.1159/000350870

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…Chromosome 9 heteromorphisms, such as the euchromatic duplication 9q13q21.1 variant, have been reported in several normal individuals. In the pericentromeric region of chromosome 9, additional copies of euchromatic segmental duplications were found in a fetus and mother [Barber et al, 2013], 2 separate extra euchromatic G+ bands were reported in a child and mother [Ozkinay et al, 2005], and an enlarged heterochromatin region in chromosome 9q was described in a normal child and numerous family members [Steffensen et al, 2009]. Since the introduction of FISH techniques, some studies have investigated the structure of chromosome 9 heteromorphisms in more detail.…”

Section: Unusual Duplication In the Pericentromericmentioning

confidence: 99%

Unusual Duplication in the Pericentromeric Region of Chromosome 9 in a Patient with Phenotypic Alterations

Malinverni

Colovati²,

Perez³

et al. 2016

Cytogenet Genome Res

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Several alterations involving the pericentromeric region of chromosome 9 are considered as normal population variants. These heterochromatic variants or heteromorphisms can include 9qh+, 9cen+, 9ph+, 9ph-, inv(9)(p11q13), and other patterns which can only be defined by FISH studies. However, some heteromorphisms have been found more frequently in patients with several clinical disorders. Here, we report on a patient with intellectual disability, language and neurodevelopmental delay, as well as facial dysmorphism and an unusual chromosome 9. While the banding karyotype was indicative of a simple pericentric inversion of one chromosome 9 [46,XX,inv(9)(p12q13)], array comparative genomic hybridization showed a 6-Mb duplication, including 22 genes: arr[hg19] 9p13.1p11.2(38,869,901- 44,870,714)×3 dn. Molecular cytogenetics using a panel of probes specific for the pericentromeric region of chromosome 9 showed an unusual, rearranged chromosome 9, der(9)(pter→p11.2::q21.11→q12::p11.2→p13.2::q12→p11.2::q21.11→qter), that has not been described before. The patient's phenotypic alterations are probably due to the de novo 6-Mb 9p duplication, although a review of similar cases showed some reports considering this duplication in the euchromatic region as a benign variant. Interestingly, this is the first report of a possible adverse inversion loop formation due to a known heteromorphic pericentric inversion present in the phenotypically normal father of the patient.

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Section: Unusual Duplication In the Pericentromericmentioning

confidence: 99%

Unusual Duplication in the Pericentromeric Region of Chromosome 9 in a Patient with Phenotypic Alterations

Malinverni

Colovati²,

Perez³

et al. 2016

Cytogenet Genome Res

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“…The C-banding was negative. This type of euchromatic variant has been reported in several cases [ 5 , 15 , 16 ] and classified as one of the four major categories of euchromatic variant [ 7 ]. The high-resolution CAM that was simultaneously performed, however, showed a genomic gain of 6.3 Mb from 9q21.33–q22.31 (chr9:90,118,500–96,395,801; hg19; Fig.…”

Section: Letter To the Editorsmentioning

confidence: 99%

Chromosomal microarray analysis as the first-tier test for the identification of pathogenic copy number variants in chromosome 9 pericentric regions and its challenge

Wang

Boyar

2016

Mol Cytogenet

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Chromosomal microarray analysis (CMA) has been recommended and practiced routinely in the large reference laboratories of U.S.A. as the first-tier test for the postnatal evaluation of individuals with intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies. Using CMA as a diagnostic tool and without a routine setting of fluorescence in situ hybridization with labeled bacterial artificial chromosome probes (BAC-FISH) in the large reference laboratories becomes a challenge in the characterization of chromosome 9 pericentric region. This region has a very complex genomic structure and contains a variety of heterochromatic and euchromatic polymorphic variants. These variants were usually studied by G-banding, C-banding and BAC-FISH analysis. Chromosomal microarray analysis (CMA) was not recommended since it may lead to false positive results. Here, we presented a cohort of four cases, in which high-resolution CMA was used as the first-tier test or simultaneously with G-banding analysis on the proband to identify pathogenic copy number variants (CNVs) in the whole genome. CMA revealed large pathogenic CNVs from chromosome 9 in 3 cases which also revealed different G-banding patterns between the two chromosome 9 homologues. Although we demonstrated that high-resolution CMA played an important role in the identification of pathogenic copy number variants in chromosome 9 pericentric regions, the lack of BAC-FISH analysis or other useful tools renders significant challenges in the characterization of chromosome 9 pericentric regions.Trial registration: None; it is not a clinical trial, and the cases were retrospectively collected and analyzed.Electronic supplementary materialThe online version of this article (doi:10.1186/s13039-016-0272-6) contains supplementary material, which is available to authorized users.

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Expansion of a 12-kb VNTR containing the REXO1L1 gene cluster underlies the microscopically visible euchromatic variant of 8q21.2

et al. 2013

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Copy number variants visible with the light microscope have been described as euchromatic variants (EVs) and EVs with extra G-light material at 8q21.2 have been reported only once before. We report four further patients with EVs of 8q21.2 ascertained for clinical (3) or reproductive reasons (1). Enhanced signal strength from two overlapping bacterial artificial chromosomes (BACs) and microarray analysis mapped the EV to a 284-kb interval in the reference genome. This interval consists of a sequence gap flanked by segmental duplications that contain the 12-kb components of one of the largest Variable Number Tandem Repeat arrays in the human genome. Using digital NanoString technology with a custom probe for the RNA exonuclease 1 homologue (S. cerevisiae)-like 1 (REXO1L1) gene within each 12-kb repeat, significantly enhanced diploid copy numbers of 270 and 265 were found in an EV family and a median diploid copy number of 166 copies in 216 controls. These 8q21.2 EVs are not thought to have clinical consequences as the phenotypes of the probands were inconsistent, those referred for reproductive reasons were otherwise phenotypically normal and the REXO1L1 gene has no known disease association. This EV was found in 4/3078 (1 in 770) consecutive referrals for chromosome analysis and needs to be distinguished from pathogenic imbalances of medial 8q. The REXO1L1 gene product is a marker of hepatitis C virus (HCV) infection and a possible association between REXO1L1 copy number and susceptibility to HCV infection, progression or response to treatment has not yet been excluded.

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

Cited by 3 publications

References 21 publications

Unusual Duplication in the Pericentromeric Region of Chromosome 9 in a Patient with Phenotypic Alterations

Unusual Duplication in the Pericentromeric Region of Chromosome 9 in a Patient with Phenotypic Alterations

Chromosomal microarray analysis as the first-tier test for the identification of pathogenic copy number variants in chromosome 9 pericentric regions and its challenge

Expansion of a 12-kb VNTR containing the REXO1L1 gene cluster underlies the microscopically visible euchromatic variant of 8q21.2

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