High resolution comparative genomic hybridisation analysis reveals imbalances in dyschromosomal patients with normal or apparently balanced conventional karyotypes

Kirchhoff, Maria; Rose, Hanne; Maahr, Jan; Gerdes, Tommy; Bugge, Merete; Tommerup, Niels; Tümer, Zeynep; Lespinasse, James; Jensen, Peter K.A.; Wirth, Jutta; Lundsteen, Claes

doi:10.1038/sj.ejhg.5200512

Cited by 48 publications

(52 citation statements)

References 13 publications

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“…However, HR-CGH analysis based on detection by standard reference intervals revealed a small 6q14.1 deletion (Fig. 4) [Kirchhoff et al, 2000]. The HR-CGH did not find in the other breakpoints chromosome segments with diminished (dim) or enhanced (enh) fluorescence intensity ratios.…”

Section: Resultsmentioning

confidence: 96%

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De novo complex chromosomal rearrangements (CCR) involving chromosome 1, 5, and 6 resulting in microdeletion for 6q14 in a female carrier with psychotic disorder

Lespinasse¹,

Bugge

Rethoré³

et al. 2004

American J of Med Genetics Pt A

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A 23-year-old obese woman with a psychotic disorder was found to have a de novo apparently balanced complex chromosomal rearrangement involving chromosomes 1, 5, and 6. Molecular cytogenetic analyses using high-resolution comparative genomic hybridization (HR-CGH) showed a microdeletion at 6q14 in a der(6). Application of HR-CGH facilitated detection of micro-rearrangement of all de novo apparently balanced complex chromosomal rearrangements (CCR) and supported the localization of the breakpoint. According to our knowledge, no constitutional interstitial microdeletion of chromosome 6q14 has been found associated with a schizoid-type phenotype.

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Section: Resultsmentioning

confidence: 96%

“…Comparative genomic hybridization (CGH) is a modified in situ hybridization method that allows comprehensive analysis of the entire genome. HR-CGH was performed as previously described [Kirchhoff et al, 2000].…”

Section: Methodsmentioning

confidence: 99%

De novo complex chromosomal rearrangements (CCR) involving chromosome 1, 5, and 6 resulting in microdeletion for 6q14 in a female carrier with psychotic disorder

Lespinasse¹,

Bugge

Rethoré³

et al. 2004

American J of Med Genetics Pt A

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“…These abnormalities are different from those we detected. Maybe these patients represent a group of dyschromosomal patients with whole genome imbalance [Kirchhoff et al, 2000] and nonspecific mental and growth retardation and dysmorphic facial features.…”

Section: Discussionmentioning

confidence: 98%

Apparently unrelated cytogenetic abnormalities among 462 probands referred for the detection of del(22q) by FISH

2002

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Laboratory-based reports of the cytogenetic abnormalities detected during the course of testing for deletion del(22q) are scant. We report our findings from the testing with FISH of 462 patients suspected to have del(22q) between 1994 and 2000. Of these, 447 had a normal karyotype. An apparently unrelated cytogenetic abnormality was detected in 15 (3.2%). Two of these abnormalities involved reciprocal translocation with chromosome 22q and one of these showed del(22q) with FISH. The other abnormalities included sex chromosome aneuploidies and unbalanced rearrangements of various chromosomal segments. There was no commonality among these abnormalities and no correlation with other reported cases. Among those with a normal karyotype, an unexpected deletion of the control arylsulphatase A (ARSA) probe was found, providing a definite frequency of 1/262 for ARSA deletions among patients suspected to have del(22q). Of the 462 referrals, 48 (10%) had one or more additional diagnoses, and in this group, 4 (8%) had del(22q) and 2 (4%) had an apparently unrelated cytogenetic abnormality. The data highlight the importance of initial cytogenetic analysis in patients suspected of del(22q) and negates the use of interphase FISH screening by itself for del(22q). The finding of 3.2% unrelated cytogenetic abnormalities is noteworthy. FISH should be used in any structural rearrangement to ascertain if the relevant locus is deleted or not. The continued reporting of patients diagnosed with del(22q) found to have an unrelated cytogenetic abnormality will expand the phenotypic spectrum and possible gene mapping may refine phenotypic specificity.

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“…[8][9][10] Indeed, it is known that approximately 6-10% of apparently balanced de novo translocations are pathogenic 31 32 and a large proportion of these are likely to be unbalanced but cannot be distinguished from true balanced translocations by conventional cytogenetic techniques. 33 Genomic deletions at a breakpoint appear to be more common than duplications. This is likely to be the result of underreporting of duplications because of the technical difficulties of detection.…”

Section: Discussionmentioning

confidence: 99%

Identification of a 650 kb duplication at the X chromosome breakpoint in a patient with 46,X,t(X;8)(q28;q12) and non-syndromic mental retardation

Cox

Holden²,

Dee³

et al. 2003

Journal of Medical Genetics

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A female patient with non-syndromic mental retardation was shown by high resolution GTL banding to have inherited an apparently balanced translocation, 46,X,t(X;8)(q28;q12)mat. Replication studies in the mother and daughter showed a skewed X inactivation pattern in lymphocytes, with the normal X chromosome preferentially inactivated. The mother also had significant intellectual disability. To investigate the possibility that a novel candidate gene for XLMR was disrupted at the X chromosome translocation breakpoint, we mapped the breakpoint using fluorescence in situ hybridisation (FISH). This showed that the four known genes involved in non-syndromic mental retardation in Xq28, FMR2, SLC6A8, MECP2, and GDI1, were not involved in the translocation. Intriguingly, we found that the X chromosome breakpoint in the daughter could not be defined by a single breakpoint spanning genomic clone and further analysis showed a 650 kb submicroscopic duplication between DXS7067 and DXS7060 on either side of the X chromosome translocation breakpoint. This duplicated region contains 11 characterised genes, of which nine are expressed in brain. Duplication of one or several of the genes within the 650 kb interval is likely to be responsible for the mental retardation phenotype seen in our patient. Xq28 appears to be an unstable region of the human genome and genomic rearrangements are recognised as major causes of two single gene defects, haemophilia A and incontinentia pigmenti, which map within Xq28. This patient therefore provides further evidence for the instability of this genomic region.

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High resolution comparative genomic hybridisation analysis reveals imbalances in dyschromosomal patients with normal or apparently balanced conventional karyotypes

Cited by 48 publications

References 13 publications

De novo complex chromosomal rearrangements (CCR) involving chromosome 1, 5, and 6 resulting in microdeletion for 6q14 in a female carrier with psychotic disorder

De novo complex chromosomal rearrangements (CCR) involving chromosome 1, 5, and 6 resulting in microdeletion for 6q14 in a female carrier with psychotic disorder

Apparently unrelated cytogenetic abnormalities among 462 probands referred for the detection of del(22q) by FISH

Identification of a 650 kb duplication at the X chromosome breakpoint in a patient with 46,X,t(X;8)(q28;q12) and non-syndromic mental retardation

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