FISH detection of Wolf‐Hirschhorn syndorem: Exclusion of D4F26 as critical site

Johnson, Virginia P.; Altherr, Michael R.; Blake, Jerome M.; Keppen, Laura Davis

doi:10.1002/ajmg.1320520114

Cited by 29 publications

(26 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6,42 We correlated the clinical findings with the size of the deletion and came to the following conclusions: cleft lip/ palate, preauricular pits/tags, and colobomata were missing in patients with deletions smaller than 9 Mb and congenital heart defects were absent in patients with deletions smaller than 16 Mb. These conclusions are supported by other reported patients with small deletions, who lacked these clinical findings, eg the patients of Albiez et al, 43 Gandelmann et al, 42 and Johnson et al 40 Johnson et al 14 hypothesised that cardiac and lip and palatal defects are due to deletions located more proximally. Fang et al 44 added renal abnormalities and hearing loss to this list.…”

Section: Discussionsupporting

confidence: 53%

See 1 more Smart Citation

Effect of the size of the deletion and clinical manifestation in Wolf-Hirschhorn syndrome: analysis of 13 patients with a de novo deletion

et al. 2000

View full text Add to dashboard Cite

We performed clinical, cytogenetic, and molecular analyses on 13 patients (8 females and 5 males, aged 6 months to 13 years) with Wolf-Hirschhorn syndrome due to de novo deletions of chromosome 4p. All patients presented with the typical facial gestalt, microcephaly, and profound mental retardation. Other clinical signs were low birth weight (10/13; 77%), postnatal short stature (8/12; 66%), muscular hypotonia (12/13; 92%), seizures (11/13; 85%), congenital heart defects (4/13; 31%), colobomata of iris (4/12; 33%), genital anomalies (4/13; 31%), deafness (3/13; 23%), and renal anomalies (3/13; 23%). The smallest deletion was a submicroscopic terminal deletion of nearly 2.5 Mb. The largest was a terminal deletion of nearly 30 Mb. Cleft lip/palate, preauricular pits/tags, and congenital heart defects were present only in patients with terminal deletions larger than 10 Mb. The deviations from mean birth weight, birth length, and postnatal head circumference correlated with the size of the deletion. Determining the parental origin of the deletion with microsatellite markers, the maternal allele was missing in three patients and the paternal allele in eight patients. Our observations support the existence of a partial genotype-phenotype correlation in Wolf-Hirschhorn syndrome.

show abstract

Section: Discussionsupporting

confidence: 53%

“…14 The aim of this study was to assess the influence of the size of the deletion on the clinical phenotype in the context of previously published reports.…”

Section: And Hirschhorn Et Almentioning

confidence: 99%

Effect of the size of the deletion and clinical manifestation in Wolf-Hirschhorn syndrome: analysis of 13 patients with a de novo deletion

et al. 2000

View full text Add to dashboard Cite

show abstract

“…The contribution of new molecular cytogenetic techniques such as fluorescence in situ hybridisation (FISH), enabled the diagnosis of WHS in patients with submicroscopic interstitial or terminal deletions or subtle unbalanced translocations (Altherr et al, 1991;Johnson et al, 1994).…”

Section: Wolf-hirschhorn Syndrome (4p-)mentioning

confidence: 99%

Cytogenetic genotype-phenotype studies: Improving genotyping, phenotyping and data storage

Feenstra

Brunner²,

Ravenswaaij³

2006

Cytogenet Genome Res

View full text Add to dashboard Cite

High-resolution molecular cytogenetic techniques such as genomic array CGH and MLPA detect submicroscopic chromosome aberrations in patients with unexplained mental retardation. These techniques rapidly change the practice of cytogenetic testing. Additionally, these techniques may improve genotype-phenotype studies of patients with microscopically visible chromosome aberrations, such as Wolf-Hirschhorn syndrome, 18q deletion syndrome and 1p36 deletion syndrome. In order to make the most of high-resolution karyotyping, a similar accuracy of phenotyping is needed to allow researchers and clinicians to make optimal use of the recent advances. International agreements on phenotype nomenclature and the use of computerized 3D face surface models are examples of such improvements in the practice of phenotyping patients with chromosomal anomalies. The combination of high-resolution cytogenetic techniques, a comprehensive, systematic system for phenotyping and optimal data storage will facilitate advances in genotype-phenotype studies and a further deconstruction of chromosomal syndromes. As a result, critical regions or single genes can be determined to be responsible for specific features and malformations.

show abstract

“…These molecular analyses were facilitated by the extensive physical maps and cloned resources available for 4p16.3 Zuo et al, 1993]. These resources have provided the foundation on which to build a molecular model for this syndrome.Previous studies excluded D4S43 and D4S142 from the critical region and defined a genomic segment of [Estabrooks et al, 1992;Gandelman et al, 1992;Johnson et al, 1994]. Owing to the abundant cloned resources from this region of the genome, a large number of potential coding sequences were identified [Gilliam et al, 1987;John et al, 1994;Rommens et al, 1993;Snell et al, 1993].…”

mentioning

confidence: 99%

“…Cosmids were chosen that spanned this area with an average distance of 560 kbp between the loci. Clones that identify the loci D4S43, FGFR3, D4S96, D4S90, and D4F26 have been utilized in previous studies [Estabrooks et al, 1992;Gandelman et al, 1992;Johnson et al, 1994]. The cosmid pC678 (D4S96) is localized telomeric to a 60 kbp gap in the clone contig [Ferrin and Camerini-Otero, 1994].…”

mentioning

confidence: 99%

Delimiting the Wolf-Hirschhorn syndrome critical region to 750 kilobase pairs

et al. 1997

Self Cite

View full text Add to dashboard Cite

Wolf-Hirschhorn syndrome (WHS) is a multiple anomaly condition characterized by mental and developmental defects, resulting from the absence of the distal segment of one chromosome 4 short arm (4p16.3). Owing to the complex and variable expression of this disorder, it is thought that the WHS is a contiguous gene syndrome with an undefined number of genes contributing to the phenotype. The 2.2 Mbp genomic segment previously defined as the critical region by the analyses of patients with terminal or interstitial deletions is extremely gene dense and an intensive investigation of the developmental role of all the genes contained within it would be daunting and expensive. Further refinement in the definition of the critical region would be valuable but depends on available patient material and accurate clinical evaluation. In this study, we have utilized fluorescence in situ hybridization to further characterize a WHS patient previously demonstrated to have an interstitial deletion and demonstrate that the distal breakpoint occurs between the loci FGFR3 and D4S168. This reduces the critical region for this syndrome to less than 750 kbp. This has the effect of eliminating several genes previously proposed as contributing to this syndrome and allows further research to focus on a more restricted region of the genome and a limited set of genes for their role in the WHS syndrome.

show abstract

FISH detection of Wolf‐Hirschhorn syndorem: Exclusion of D4F26 as critical site

Cited by 29 publications

References 15 publications

Effect of the size of the deletion and clinical manifestation in Wolf-Hirschhorn syndrome: analysis of 13 patients with a de novo deletion

Effect of the size of the deletion and clinical manifestation in Wolf-Hirschhorn syndrome: analysis of 13 patients with a de novo deletion

Cytogenetic genotype-phenotype studies: Improving genotyping, phenotyping and data storage

Delimiting the Wolf-Hirschhorn syndrome critical region to 750 kilobase pairs

Contact Info

Product

Resources

About