Beckwith-Wiedemann syndrome and assisted reproduction technology (ART).
نویسندگان
چکیده
Beckwith-Wiedemann syndrome (BWS) is a model imprinting disorder resulting from mutations or epimutations affecting imprinted genes on chromosome 11p15.5. The classical clinical features of BWS are macroglossia, preand/or postnatal overgrowth, and anterior abdominal wall defects (umbilical hernia or exomphalos). Additional more variable features include hemihypertrophy, neonatal hypoglycaemia, facial naevus flammeus, ear pits and creases, renal anomalies, and an increased risk of embryonal tumours. Most cases of BWS are sporadic and ∼20% of these have uniparental disomy (paternal isodisomy) for a variable region of chromosome 11 which always includes the 11p15.5 imprinted gene cluster. Up to 60% of sporadic BWS patients have epigenetic changes at differentially methylated regions within 11p15.5 that are associated with alterations in the imprinting or expression of paternally expressed genes, such as IGF2 and KCNQ1OT, or maternally expressed genes, such as H19 and CDKN1C. Thus, 5-10% have epigenetic alterations at the IGF2/H19 loci (the maternal H19 and IGF2 alleles display paternal allele methylation and expression patterns with biallelic IGF2 expression and silencing of H19 expression), and 40-50% have loss of maternal allele methylation at a differentially methylated region (KvDMR1) within an intron of KCNQ1. KvDMR1 loss of methylation is associated with biallelic expression of KCNQ1OT. The epigenetic alterations at H19/IGF2 or KvDMR1 are thought to result from defects at two putative imprinting control centres (BWSIC1 and BWSIC2, respectively). The precise nature of the putative BWSIC2 is unknown and therefore the origin of these putative BWSIC2 defects is unknown. Weksberg et al showed a clear association between monozygotic twinning and BWS with KvDMR1 loss of methylation and suggested two possible explanations: (1) that discordance for BWS in monozygotic twins is caused by unequal splitting of the inner cell mass during twinning resulting in differential maintenance of imprinting at KvDMR1, or (2) that loss of imprinting associated with KvDMR1 demethylation predisposes to twinning as well as to discordance for BWS. Recently, a possible association between another human imprinting disorder, Angelman syndrome, and intracytoplasmic sperm injection (ICSI) was reported. Angelman syndrome occurs in ∼1 in 15 000 newborns and most cases have a deletion of 15q. Although only a minority of cases (<5%) of Angelman syndrome are caused by an imprinting defect, 14 both of the two cases associated with ICSI that were described by Cox et al had an imprinting defect. This led to the suggestion that ICSI may be associated with an increased susceptibility to imprinting errors. To investigate this hypothesis further, we have determined whether there is evidence of an association between BWS and a history of assisted conception techniques.
منابع مشابه
Epigenetic risks related to assisted reproductive technologies: epigenetics, imprinting, ART and icebergs?
Recently, a series of case reports and small studies has suggested that births involving assisted reproductive technology (ART) may have an increased risk of imprinting disorders such as Beckwith-Wiedemann syndrome and Angelman syndrome. Herein, the significance and implications of these findings are discussed. It is speculated that, although such imprinting disorders may be shown to be only ra...
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An association between assisted reproduction technologies (ART) and abnormal genomic imprinting in humans has been recognized for several years; however, the magnitude of this risk and the spectrum of imprinting syndromes to which the risk applies remains unknown. Nine human imprinting syndromes have been identified but current evidence links ART with only three: Beckwith-Wiedemann syndrome, An...
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Recent data in humans and animals suggest that assisted reproductive technology (ART) might affect the epigenetics of early embryogenesis and might cause birth defects. We report the first evidence, to our knowledge, that ART is associated with a human overgrowth syndrome-namely, Beckwith-Wiedemann syndrome (BWS). In a prospective study, the prevalence of ART was 4.6% (3 of 65), versus the back...
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Beckwith Wiedemann Syndrome (BWS) is a rare congenital disease of low prevalence. However, it presents a high prevalence within the genetic pathologies of overgrowth. This syndrome presents typical manifestations such as macroglossia, macrosomy at birth, omphalocele and defects of the anterior abdominal wall. Its origin is known to be genetic, but its mechanism of generation is not clear. This ...
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BACKGROUND Genomic imprinting is an epigenetic process in which allele-specific gene expression is dependent on the parental inheritance. Although only a minority of human genes are imprinted, those that have been identified to date have been preferentially implicated in prenatal growth and neurodevelopment. Mutations or epimutations in imprinted genes or imprinting control centres are associat...
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عنوان ژورنال:
- Journal of medical genetics
دوره 40 1 شماره
صفحات -
تاریخ انتشار 2003