Parental origin of chromosome 4p deletion in Wolf‐Hirschhorn syndrome

Dallapiccola, Bruno; Mandich, Paola; Bellone, Emilia; Selicorni, Angelo; Mokin, Vahe; Ajmar, Franco; Novelli, Giuseppe

doi:10.1002/ajmg.1320470622

Cited by 48 publications

(24 citation statements)

References 20 publications

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“…12,13 De novo 4p deletions are reasonably assumed to be single chromosome anomalies. However, unbalanced de novo translocations, above all t(4;8)(p16.1;p23) translocations, were detected recently with an unexpectedly high frequency in WHS 10,14,15 and, whenever investigated, they were of maternal origin.…”

Section: Discussionmentioning

confidence: 99%

“…1,3 -11 Although the severity of the clinical presentation usually correlates with the size of the deletion, phenotypic variability represents a hallmark of this condition, suggesting the role of other factors in the determination of the phenotype. De novo 4p rearrangements more often occur in paternal meiosis 12,13 and are largely assumed to be isolated deletions. However, unbalanced de novo t(4p;8p) translocations have been detected with unexpected high frequency in WHS patients and, whenever tested, they were maternal in origin.…”

Section: Introductionmentioning

confidence: 99%

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A double cryptic chromosome imbalance is an important factor to explain phenotypic variability in Wolf–Hirschhorn syndrome

Zollino¹,

Lecce²,

Selicorni

et al. 2004

Eur J Hum Genet

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A total of five Wolf-Hirschhorn syndrome (WHS) patient with a 4p16.3 de novo microdeletion was referred because of genotype -phenotype inconsistencies, first explained as phenotypic variability of the WHS. The actual deletion size was found to be about 12 Mb in three patients, 5 Mb in another one and 20 Mb in the last one, leading us to hypothesize the presence of an extrachromosome segment on the deleted 4p. A der(4)(4qter-p16.1::8p23-pter) chromosome, resulting from an unbalanced de novo translocation was, in fact, detected in four patients and a der(4)(4qter-q32::4p15.3-qter) in the last. Unbalanced t(4;8) translocations were maternal in origin, the rec(4p;4q) was paternal. With the purpose of verifying frequency and specificity of this phenomenon, we investigated yet another group of 20 WHS patients with de novo large deletions (n ¼ 13) or microdeletions (n ¼ 7) and with apparently straightforward genotypephenotype correlations. The rearrangement was paternal in origin, and occurred as a single anomaly in 19 out of 20 patients. In the remaining patient, the deleted chromosome 4 was maternally derived and consisted of a der(4)(4qter-4p16.3::8p23-8pter). In conclusions, we observed that 20% (5/25) of de novo WHS-associated rearrangements were maternal in origin and 80% (20/25) were paternal. All the maternally derived rearrangements were de novo unbalanced t(4;8) translocations and showed specific clinical phenotypes. Paternally derived rearrangements were usually isolated deletions. It can be inferred that a double, cryptic chromosome imbalance is an important factor for phenotypic variability in WHS. It acts either by masking the actual deletion size or by doubling a quantitative change of the genome.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A double cryptic chromosome imbalance is an important factor to explain phenotypic variability in Wolf–Hirschhorn syndrome

Zollino¹,

Lecce²,

Selicorni

et al. 2004

Eur J Hum Genet

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“…In about 85 % of cases with partial deletion in chromosome 18q, this chromosome is paternally derived (Cody et al, 1997). Moreover, 80 % of the cases with Wolf-Hirschhorn syndrome (4p -) and 80-90 % of cases with cri-du-chat syndrome (5p -) originate in the male germ line (Overhauser et al, 1990;Dallapiccola et al, 1993;Wieczorek et al, 2000;Mainardi et al, 2001). Various studies have been performed to examine the relationship between paternal age and the incidence of de novo structural chromosome rearrangements in newborns and fetuses with dissenting results (Resseguie, 1976;Selvin and Garfinkel, 1976;Chamberlin and Magenis, 1980;Hook, 1984;Hook and Cross, 1987).…”

Section: Epidemiological Studiesmentioning

confidence: 99%

Effect of paternal age on the frequency of cytogenetic abnormalities in human spermatozoa

Buwe

Guttenbach²,

Schmid³

2005

Cytogenet Genome Res

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Many surveys have been performed to find etiological relationships between pregnancy outcome and specific risk factors, such as exposure to chemicals and radiation or parental age. Advanced maternal age is a strong risk factor for trisomic pregnancies, albeit there are considerable variations among the different chromosomes. The definite incidence of the various structural and numerical chromosome aberrations in spontaneous abortions and liveborns is well known, as well as the rate of maternally and paternally derived rearrangements. Nevertheless studies have failed to assert an age-dependent risk for men fathering chromosomally abnormal children. New techniques using fluorescence in situ hybridization render it possible to analyze spermatozoa directly for numerical and, to some extent, for structural aberrations. This article compiles the findings of studies on human spermatozoa over the last few years.

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“…The majority of 115 de novo unbalanced structural chromosome abnormalities detectable by light microscopy are of paternal origin 4 varying from 84% of interstitial deletions to 58% of duplications and rings. Deletions of the long arm of chromosome 18 are disproportionately male 5 as well as the deletions that cause Wolf-Hirschhorn syndrome 6 and Cri-du-chat syndrome. 7 More recently, the parental origin of de novo microdeletions associated with de novo reciprocal translocations and cases of complex chromosomes rearrangements was determined to be paternal in all cases.…”

Section: Introductionmentioning

confidence: 99%

Advanced age increases chromosome structural abnormalities in human spermatozoa

et al. 2010

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This study explores the relationship between sperm structural aberrations and age by using a multicolor multichromosome FISH strategy that provides information on the incidence of duplications and deletions on all the autosomes. ToTelvysion kit (Abbott Molecular, Abbott Park, IL, USA) with telomere-specific probes was used. We investigated the sperm of 10 male donors aged from 23 to 74 years old. The donors were divided into two groups according to age, a cohort of five individuals younger than 40 and a cohort of five individuals older than 60 years. The goal of this study was to determine (1) the relationship between donor age and frequency and type of chromosome structural abnormalities and (2) chromosomes more frequently involved in sperm structural aberrations. We found that the older patients had a higher rate of structural abnormalities (6.6%) compared with the younger cohort (4.9%). Although both duplications and deletions were seen more frequently in older men, our findings demonstrate the presence of an excess of duplications versus deletions in both groups at a ratio of 2 to 1. We demonstrate that the distribution of duplications and deletions was not linear along the chromosomes, although a trend toward a higher rate of abnormalities in larger chromosomes was observed. This work is the first study addressing the frequencies of sperm chromosome structural aberrations of all autosomes in a single assay thus making a contribution to the clarification of the amount and origin of damage present in human spermatozoa and in relation to age.

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Parental origin of chromosome 4p deletion in Wolf‐Hirschhorn syndrome

Cited by 48 publications

References 20 publications

A double cryptic chromosome imbalance is an important factor to explain phenotypic variability in Wolf–Hirschhorn syndrome

A double cryptic chromosome imbalance is an important factor to explain phenotypic variability in Wolf–Hirschhorn syndrome

Effect of paternal age on the frequency of cytogenetic abnormalities in human spermatozoa

Advanced age increases chromosome structural abnormalities in human spermatozoa

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