Paternal origin of the chromosomal deletion resulting in Wolf-Hirschhorn syndrome.

Quarrell, Oliver; Snell, Russell G.; Curtis, M. A.; Roberts, Susan; Ps, Harper; Shaw, Duncan

doi:10.1136/jmg.28.4.256

Cited by 34 publications

(21 citation statements)

References 23 publications

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“…11 De novo events are estimated to occur in 85-87% of WHS patients 10 and here the paternally derived deletions are more frequent. 12,13 Here, we evaluate 13 WHS patients with de novo deletions by clinical, cytogenetic, and molecular analyses to assess the severity of the clinical phenotype in context of the size and origin of the deletion.…”

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

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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.

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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

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“…The Wolf-Hirschhorn syndrome (WHS), caused by a deletion of the short arm of chromosome 4, is a rare condition, the incidence of which has been estimated to be around 1/50,000 to 1/95,896 births [2,3]. According to Lurie et al [4], 75% of patients with WHS will have a de novo documented deletion of 4p, the origin of which is paternal in 85% of cases [5,6]. About 12% will have an unusual cytogenetic situation, such as a ring 4 chromosome, mosaicism of the 4p-, or a sporadic unbalanced translocation.…”

Section: Introductionmentioning

confidence: 99%

Prenatal Sonographic Patterns in Six Cases of Wolf-Hirschhorn (4p–) Syndrome

Boog¹,

Vaillant²,

Collet

et al. 2004

Fetal Diagn Ther

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This multicentric study presents 6 cases of Wolf-Hirschhorn syndrome (deletion of 4p) detected after a sonographic prenatal diagnosis of early intrauterine growth retardation with fetal abnormalities. Standard karyotyping on regular G-banding during pregnancy was normal in half of the cases. Fortunately, the associated sonographic signs of a typical face, cystic cerebral lesions, midline fusion defects and bilateral renal hypoplasia may help to refine specific indications for high-resolution banding and molecular analysis by in situ hybridization.

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“…The origin was paternal in 32 (75%) and maternal in 8 (25%) cases [8][9][10][28][29][30][31][32][33]. Genomic imprinting has been considered a mechanism to explain the excessive paternal origin of WHS [8,9]. However, the excess of maternally derived 4p deletions due to familial translocations that resulted in WHS indistinguishable from the de novo cases is against this hypothesis [34].…”

Section: Discussionmentioning

confidence: 92%

“…Including our case, parental origin is determined in a total of 40 patients with WHS carrying a de novo terminal deletion without associated other structural imbalances. The origin was paternal in 32 (75%) and maternal in 8 (25%) cases [8][9][10][28][29][30][31][32][33]. Genomic imprinting has been considered a mechanism to explain the excessive paternal origin of WHS [8,9].…”

Section: Discussionmentioning

confidence: 99%

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Clinical, Cytogenetic and Molecular Investigation in a Fetus with Wolf-Hirschhorn Syndrome with Paternally Derived 4p Deletion

Dietze

Fritz²,

Huhle³

et al. 2004

Fetal Diagn Ther

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Wolf-Hirschhorn (4p-) syndrome (WHS), caused by partial deletion of the short arm of chromosome 4, has been extensively described in children and young adults. Knowledge on fetuses with WHS is still limited due to the small number of published cases. We report on a fetus with prenatally diagnosed severe intrauterine growth retardation, reduced thoracal diameter, clubfeet deformity and midface hypoplasia including slight microretrognathia indicative for fetal karyotyping. Chromosome analysis after amniocentesis revealed a de novo terminal deletion of chromosome 4p [karyotype: 46,XX,del(4) (p16)] which was confirmed by FISH. Analyses of a set of polymorphic markers mapping in 4pter->4p15.3 showed absence of paternal haplotypes. These observations corroborate the preferential paternal origin of the de novo 4p deletion in WHS patients. Furthermore, the distal breakpoint could be narrowed to band 4p16.1. At autopsy, the fetus showed typical craniofacial dysmorphic signs of WHS, severe IUGR and delayed bone age. This report suggests the possibility of recognising the particular phenotype of WHS in utero by prenatal ultrasound and emphasises the importance of karyotyping fetuses with severe IUGR, especially when the amount of amniotic fluid is normal.

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Paternal origin of the chromosomal deletion resulting in Wolf-Hirschhorn syndrome.

Abstract: DNA samples were obtained from children with

Cited by 34 publications

References 23 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

Prenatal Sonographic Patterns in Six Cases of Wolf-Hirschhorn (4p–) Syndrome

Clinical, Cytogenetic and Molecular Investigation in a Fetus with Wolf-Hirschhorn Syndrome with Paternally Derived 4p Deletion

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