Prospective study comparing HR‐CGH and subtelomeric FISH for investigation of individuals with mental retardation and dysmorphic features and an update of a study using only HR‐CGH

Kirchhoff, Maria; Pedersen, Søren; Kjeldsen, Eigil; Rose, Hanne; Dunø, Morten; Kølvraa, Steen; Lundsteen, Claes

doi:10.1002/ajmg.a.20678

Cited by 35 publications

(31 citation statements)

References 40 publications

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“…High-resolution chromosome analysis in Patient 1 and high-resolution CGH in Patient 2 were both normal. High-resolution CGH detects cryptic deletions or duplications !2.5 Mb [Kirchhoff et al, 2004].…”

Section: Discussionmentioning

confidence: 99%

Autosomal dominant syndrome resembling Coffin–Siris syndrome

Flynn

Milunsky

2006

American J of Med Genetics Pt A

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Coffin-Siris syndrome is a multiple congenital anomaly/mental retardation syndrome with phenotypic variability [OMIM 135900]. The diagnosis is based solely on clinical findings, as there is currently no molecular, biochemical, or cytogenetic analysis available to confirm a diagnosis. Although typically described as an autosomal recessive disorder, autosomal dominant inheritance has also been infrequently reported. We describe a mother and her two daughters who all have features that resemble Coffin-Siris syndrome. However, this is not a completely convincing diagnosis given that hypertelorism is not a feature of Coffin-Siris syndrome and the family is relatively mildly affected. Yet, this family provides further evidence of an autosomal dominant mode of inheritance for a likely variant of Coffin-Siris syndrome (at least in some families). In addition, Sibling 1 had premature thelarche. She is the second reported individual within the spectrum of Coffin-Siris syndrome to have premature thelarche, indicating that it may be a rare clinical feature.

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Section: Discussionmentioning

confidence: 99%

Autosomal dominant syndrome resembling Coffin–Siris syndrome

Flynn

Milunsky

2006

American J of Med Genetics Pt A

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“…Even though the deleted region seen in case 3 overlaps with several genomic variants reported in controls in the Database of Genomic Variants the combination of this deletion with the translocation may be involved in the patient's phenotype. De novo deletions at chromosome 7q22 have previously been reported in children with mental retardation and dysmorphic features using CGH on high-resolution chromosomes and array CGH (Kirchhoff et al, 2004;KrepischiSantos et al, 2006). The deletion identified in case 3 partially overlaps with the deletion detected in a 14-year-old female with developmental delay, mild mental retardation, abdominal obesity, hyperphagia and hypothyroidism (Krepischi-Santos et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

A 1q44 deletion, paternal UPD of chromosome 2 and a deletion due to a complex translocation detected in children with abnormal phenotypes using new SNP array technology

Talseth‐Palmer

Meldrum

Nicholl

et al. 2009

Cytogenet Genome Res

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Children with intellectual disability, dysmorphic features, malformations and/or growth abnormalities frequently display normal karyotypes. Recent studies have shown that genome-wide single nucleotide polymorphism (SNP) arrays can be effective in detecting abnormalities involving copy number variation (CNV), deletions, duplications and loss of heterozygosity (LOH) that routine cytogenetic tests fail to identify. Five patients with various degrees of intellectual disability and/or dysmorphic features and other malformations were whole-genome genotyped using the Human-1 Genotyping BeadChip – Exon-Centrix 100K SNP arrays (Illumina). All patients had undergone routine cytogenetic testing; four patients had normal karyotypes, while one patient had an apparently balanced complex translocation involving chromosomes 1q25, 1q32, 2q23, 7q22 and 16q24. We detected deletions on chromosome 1q44 and 13q31.1 in one patient, and LOH of the entire chromosome 2 in another patient, both with cytogenetically normal karyotypes. The patient with the complex translocation had a deletion on chromosome 7q22.2-22.3, which is in conjunction with one of the translocation breakpoints. Our findings provide further evidence of there being a critical region for the development of microcephaly and corpus callosum abnormalities in children with distal 1q deletions. We have also shown that apparently balanced complex translocations might not be balanced at the DNA level, and we report the fourth case of paternal uniparental disomy of chromosome 2. The results of this study suggest that it may be desirable to investigate idiopathic mental retardation using genome-wide SNP arrays, in conjunction with other cytogenetic and molecular techniques.

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“…In all but four cases, the imbalances were analysed and verified by HR-CGH (Kirchhoff et al, 1999(Kirchhoff et al, , 2004. As controls we included three patients with known genomic disorders, i.e., Smith-Magenis syndrome (SMS) (case 16), Prader-Willi/Angelman syndrome (case 15) and 22q11 deletion/DiGeorge syndrome (case 7), respectively.…”

Section: Patient Samplesmentioning

confidence: 99%

Impact of low copy repeats on the generation of balanced and unbalanced chromosomal aberrations in mental retardation

Erdogan

Chen

Kirchhoff

et al. 2006

Cytogenet Genome Res

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Low copy repeats (LCRs) are stretches of duplicated DNA that are more than 1 kb in size and share a sequence similarity that exceeds 90%. Non-allelic homologous recombination (NAHR) between highly similar LCRs has been implicated in numerous genomic disorders. This study aimed at defining the impact of LCRs on the generation of balanced and unbalanced chromosomal rearrangements in mentally retarded patients. A cohort of 22 patients, preselected for the presence of submicroscopic imbalances, was analysed using submegabase resolution tiling path array CGH and the results were compared with a set of 41 patients with balanced translocations and breakpoints that were mapped to the BAC level by FISH. Our data indicate an accumulation of LCRs at breakpoints of both balanced and unbalanced rearrangements. LCRs with high sequence similarity in both breakpoint regions, suggesting NAHR as the most likely cause of rearrangement, were observed in 6/22 patients with chromosomal imbalances, but not in any of the balanced translocation cases studied. In case of chromosomal imbalances, the likelihood of NAHR seems to be inversely related to the size of the aberration. Our data also suggest the presence of additional mechanisms coinciding with or dependent on the presence of LCRs that may induce an increased instability at these chromosomal sites.

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Prospective study comparing HR‐CGH and subtelomeric FISH for investigation of individuals with mental retardation and dysmorphic features and an update of a study using only HR‐CGH

Cited by 35 publications

References 40 publications

Autosomal dominant syndrome resembling Coffin–Siris syndrome

Autosomal dominant syndrome resembling Coffin–Siris syndrome

A 1q44 deletion, paternal UPD of chromosome 2 and a deletion due to a complex translocation detected in children with abnormal phenotypes using new SNP array technology

Impact of low copy repeats on the generation of balanced and unbalanced chromosomal aberrations in mental retardation

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