Genetic and clinical studies in 13 patients with the Wolf-Hirschhorn syndrome [del(4p)]

Wilson, Miriam G.; Towner, Joseph W.; Coffin, Grange S.; Ebbin, Allan J.; Siris, Evelyn; Brager, Paul

doi:10.1007/bf00295461

Cited by 107 publications

(64 citation statements)

References 25 publications

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“…Female liveborn WHS patients are more frequent than males, which has been documented in all reviews. An average 39 weeks gestation at birth in our group of patients agrees with the data of Wilson et al 3 Birth weight ranged from 1580 g (patient 3) to 2750 g (patient 4) in our patients consistent with all reviews estimating an average birth weight of 2000 g (Table 2). Head circumference at birth is microcephalic with 31 cm in most of our WHS patients and in those described in the literature.…”

Section: Discussionsupporting

confidence: 92%

“…3,10 The rate of familial translocations in WHS patients has been reported to be up to 15%, 10 66% of them maternally inherited. 11 De novo events are estimated to occur in 85-87% of WHS patients 10 and here the paternally derived deletions are more frequent.…”

Section: And Hirschhorn Et Almentioning

confidence: 99%

“…[3][4][5] The minimal critical region has been narrowed down to 165 kb in the chromosomal band 4p16.3. 6 Potential candidate genes such as WHSC1, WHSC2, and LETM1 have been identified.…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 92%

Section: And Hirschhorn Et Almentioning

confidence: 99%

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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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“…Cardiac evaluation may include clinical examination with a stethoscope to evaluate heart and lung sounds, x-ray studies, tests that record the electrical activities of the heart muscle, a technique in which sound waves are directed toward the heart, enabling evaluation of cardiac motion and function, or other measures (e.g., cardiac catheterization). The large variability of the phenotype in trisomy 4p may be explained by the variation in length of the duplicated segments [11,12].…”

Section: Balkan Journal Of Medical Geneticsmentioning

confidence: 99%

Clinical Manifestations of Partial Trisomy 4p

Demırhan

Özgünen

Taştemir

2010

Balkan Journal of Medical Genetics

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We made the diagnosis prenatally from cytogenetic analysis of amniocytes cultured following amniocentesis performed at 20 weeks' gestation on a woman in whom ultrasound examination of the female fetus showed severe growth retardation, lung and kidney hypoplasia, and a congenital heart defect. Analysis revealed a de novo trisomy of the terminal short arm of chromosome 4 (4p16.1-pter). The parents opted to terminate the pregnancy. Fetopathological examination showed dysmorphic features and other abnormalities consistent with clinical manifestations of partial trisomy 4p.

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“…The phenotypic presentation includes a "Greek warrior helmet" facial appearance (prominent glabella, hypertelorism, widely set eyes), various midline closure defects, growth retardation, juvenile seizures, cataracts, iris colobomas, and mental retardation (Lurie et al, 1980;Wilson et al, 1981). Utilizing nested deletions generated by ES cell irradiation (You et al, 1997), five mouse models with different sized deletions in the mouse chromosome 5 (in a region of conserved synteny with human 4p16.3) were produced (Naf et al, 2001).…”

Section: Wolf-hirschhorn Syndromementioning

confidence: 99%

Animal models for human contiguous gene syndromes and other genomic disorders

2004

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Genomic disorders refer to a group of syndromes caused by DNA rearrangements, such as deletions and duplications, which result in an alteration of normal gene dosage. The chromosomal rearrangements are usually relatively small and often difficult to detect cytogenetically. In a subset of such conditions the rearrangements comprise multiple unrelated contiguous genes that are physically linked and thus have been referred to as contiguous gene syndromes (CGS). In general, each syndrome presents a complex clinical phenotype that has been attributed generally to dosage sensitive gene(s) present in the responsible chromosomal interval. A common mechanism for CGS resulting from interstitial deletion/duplication has recently been elucidated. The DNA rearrangements result from nonallelic homologous recombination (NAHR) utilizing flanking low-copy repeats (LCRs) as recombination substrates. The resulting rearrangements often involve the same genomic region, a common deletion or duplication, making it difficult to assign a specific phenotype or endophenotype to a single responsible gene. The human and mouse genome sequencing projects, in conjunction with the ability to engineer mouse chromosome rearrangements, have enabled the production of mouse models for CGS and genomic disorders. In this review we present an overview of different techniques utilized to generate mouse models for selected genomic disorders. These models foment novel insights into the specific genes that convey the phenotype by dosage and/or position effects and provide opportunities to explore therapeutic options.

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Genetic and clinical studies in 13 patients with the Wolf-Hirschhorn syndrome [del(4p)]

Cited by 107 publications

References 25 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

Clinical Manifestations of Partial Trisomy 4p

Animal models for human contiguous gene syndromes and other genomic disorders

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