Mild Wolf-Hirschhorn syndrome: micro-array CGH analysis of atypical 4p16.3 deletions enables refinement of the genotype-phenotype map

Buggenhout, Griet Van

doi:10.1136/jmg.2003.016865

Cited by 115 publications

(113 citation statements)

References 24 publications

(23 reference statements)

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“…This was corroborated by array-CGH, which demonstrated a terminal 8.3 Mb deletion of 4p covering both the WHSCR1 and WHSCR2 regions and including all the genes deemed to be involved in the development of the core features of WHS and additional midline defects. 3,4 As our patient does not show some of the characteristic midline defects of WHS while being hemizygous for the WHSC1, WHSC2, LETM1, FGFR3, TACC3 (also known as AINT), SLBP, HDNTNP, and HSPX153 loci, we conclude that mere hemizygosity for these genes does not suffice to explain the phenotype of our patient. 1,3 The presence of a 2.6 Mb duplication immediately adjacent to the 8.3 Mb deletion of chromosome 4pter-p16 prompted us to consider a potential contribution of a secondary chromosome imbalance, possibly associated with a cryptic chromosome translocation.…”

Section: Discussionmentioning

confidence: 79%

Unmasking of a hemizygous WFS1 gene mutation by a chromosome 4p deletion of 8.3 Mb in a patient with Wolf–Hirschhorn syndrome

et al. 2007

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Section: Discussionmentioning

confidence: 79%

Unmasking of a hemizygous WFS1 gene mutation by a chromosome 4p deletion of 8.3 Mb in a patient with Wolf–Hirschhorn syndrome

et al. 2007

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“…We hybridized the slides for 48 h under coverslips in a humid chamber saturated with 20% formamide and 2Â saline sodium citrate. We carried out posthybridization washes and image and data analysis as described 24 . Spot intensities were corrected for the local background.…”

Section: Methodsmentioning

confidence: 99%

Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia

et al. 2004

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“…29 There are four clusters of OR genes on 4p at 3.9, 4.2, 9.1, and 9.4 Mb from 4pter; 30 regions that coincide with our clusters of 4p breakpoints. There are also OR gene clusters on 8p at 7.1, 7.4, 7.6, and 7.9 Mb from 8pter as well as on 11p at 3.4, 3.6, 4.1, and 5.0 Mb from 11pter.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of Wolf–Hirschhorn syndrome using array CGH indicates a high prevalence of translocations

et al. 2007

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Wolf-Hirschhorn syndrome (WHS) is caused by deletions involving chromosome region 4p16.3. The minimal diagnostic criteria include mild-to-severe mental retardation, hypotonia, growth delay and a distinctive facial appearance. Variable manifestations include feeding difficulties, seizures and major congenital anomalies. Clinical variation may be explained by variation in the size of the deletion. However, in addition to having a deletion involving 4p16.3, previous studies indicate that approximately 15% of WHS patients are also duplicated for another chromosome region due to an unbalanced translocation. It is likely that the prevalence of unbalanced translocations resulting in WHS is underestimated since they can be missed using conventional chromosome analyses such as karyotyping and WHS-specific fluorescence in situ hybridization (FISH). Therefore, we hypothesized that some of the clinical variation may be due to an unrecognized and unbalanced translocation. Array comparative genomic hybridization (aCGH) is a new technology that can analyze the entire genome at a significantly higher resolution over conventional cytogenetics to characterize unbalanced rearrangements. We used aCGH to analyze 33 patients with WHS and found a much higher than expected frequency of unbalanced translocations (15/33, 45%). Seven of these 15 cases were cryptic translocations not detected by a previous karyotype combined with WHS-specific FISH. Three of these 15 cases had an unbalanced translocation involving the short arm of an acrocentric chromosome and were not detected by either aCGH or subtelomere FISH. Analysis of clinical manifestations of each patient also revealed that patients with an unbalanced translocation often presented with exceptions to some expected phenotypes.

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Mild Wolf-Hirschhorn syndrome: micro-array CGH analysis of atypical 4p16.3 deletions enables refinement of the genotype-phenotype map

Cited by 115 publications

References 24 publications

Unmasking of a hemizygous WFS1 gene mutation by a chromosome 4p deletion of 8.3 Mb in a patient with Wolf–Hirschhorn syndrome

Unmasking of a hemizygous WFS1 gene mutation by a chromosome 4p deletion of 8.3 Mb in a patient with Wolf–Hirschhorn syndrome

Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia

Comprehensive analysis of Wolf–Hirschhorn syndrome using array CGH indicates a high prevalence of translocations

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