Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Medical Genetics
Published in: BMC Medical Genetics 1/2017

Open Access 01-12-2017 | Research article

Sequence variants identification at the KCNQ1OT1:TSS differentially Methylated region in isolated omphalocele cases

Authors: Maria Francesca Bedeschi, Mariarosaria Calvello, Leda Paganini, Lidia Pezzani, Marco Baccarin, Laura Fontana, Silvia M. Sirchia, Silvana Guerneri, Lorena Canazza, Ernesto Leva, Lorenzo Colombo, Faustina Lalatta, Fabio Mosca, Silvia Tabano, Monica Miozzo

Published in: BMC Medical Genetics | Issue 1/2017

Login to get access

Abstract

Background

Omphalocele is a congenital midline ventral body wall defect that can exist as isolated malformation or as part of a syndrome. It can be considered one of the major and most frequent clinical manifestation of Beckwith-Wiedemann Syndrome (BWS) in case of loss of methylation at KCNQ1OT1: Transcription Star Site-Differentially Methylated Region (TSS-DMR) or in presence of CDKN1C mutations. The isolated form of the omphalocele accounts approximately for about the 14% of the total cases and its molecular etiology has never been fully elucidated.

Methods

Given the tight relationship with BWS, we hypothesized that the isolated form of the omphalocele could belong to the heterogeneous spectrum of the BWS associated features, representing an endophenotype with a clear genetic connection. We therefore investigated genetic and epigenetic changes affecting BWS imprinted locus at 11p15.5 imprinted region, focusing in particular on the KCNQ1OT1:TSS DMR.

Results

We studied 21 cases of isolated omphalocele detected during pregnancy or at birth and identified the following rare maternally inherited variants: i) the non-coding variant G > A at nucleotide 687 (NR_002728.3) at KCNQ1OT1:TSS-DMR, which alters the methylation pattern of the imprinted allele, in one patient; ii) the deletion c.624-629delGGCCCC at exon 1 of CDKN1C, with unknown clinical significance, in two unrelated cases.

Conclusions

Taken together, these findings suggest that KCNQ1OT1:TSS-DMR could be a susceptibility locus for the isolated omphalocele.
Appendix
Available only for authorised users
Literature
1.
Sadler TW. The embryologic origin of ventral body wall defects. Semin Pediatr Surg. 2010;19(3):209–14.CrossRefPubMed
2.
Cohen-Overbeek TE, Tong WH, Hatzmann TR, Wilms JF, Govaerts LC, Galjaard RJ, et al. Omphalocele: comparison of outcome following prenatal or postnatal diagnosis. Ultrasound Obstet Gynecol. 2010;36(6):687–92.CrossRefPubMed
3.
Hoyme HE, Higginbottom MC, Jones KL. The vascular pathogenesis of gastroschisis: intrauterine interruption of the omphalomesenteric artery. J Pediatr. 1981;98(2):228–31.CrossRefPubMed
4.
Brewer S, Williams T. Loss of AP-2a impacts multiple aspects of ventral body wall development and closure. Dev Biol. 2004;267(2):399–417.CrossRefPubMed
5.
Brewer S, Williams T. Finally, a sense of closure? Animal models of human ventral body wall defects. BioEssays. 2004;26(12):1307–21.CrossRefPubMed
6.
Prefumo F, Izzi C. Fetal abdominal wall defects. Best Pract Res Clin Obstet Gynaecol. 2014;28(3):391–402.CrossRefPubMed
7.
Chen CP. Syndromes and disorders associated with omphalocele (I): Beckwith-Wiedemann syndrome. Taiwan J Obstet Gynecol. 2007;46(2):96–102.CrossRefPubMed
8.
Chen CP. Syndromes and disorders associated with omphalocele (II): OEIS complex and Pentalogy of Cantrell. Taiwan J Obstet Gynecol. 2007;46(2):103–10.CrossRefPubMed
9.
Chen CP. Syndromes and disorders associated with omphalocele (III): single gene disorders, neural tube defects, diaphragmatic defects and others. Taiwan J Obstet Gynecol. 2007;46(2):111–20.CrossRefPubMed
10.
Frolov P, Alali J, Klein MD. Clinical risk factors for gastroschisis and omphalocele in humans: a review of the literature. Pediatr Surg Int. 2010;26(12):1135–48.CrossRefPubMed
11.
Bliek J, Maas S, Alders M, Merks JH, Mannens M. Epigenotype, phenotype and tumors in patients with isolated hemihyperplasia. J Pediatr. 2008;153(1):95–100.CrossRefPubMed
12.
Martin RA, Grange DK, Zehnbauer B, Debaun MR. LIT1 and H19 methylation defects in isolated hemihyperplasia. Am J Med Genet. 2005;134:129–31.CrossRef
13.
Cerrato F, De Crescenzo A, Riccio A. Looking for CDKN1C enhancers. Eur J Hum Genet. 2014;22(4):442–3.CrossRefPubMed
14.
Milani D, Pezzani L, Tabano S, Miozzo M. Beckwith-Wiedemann and IMAGe syndromes: two very different diseases caused by mutations on the same gene. Appl Clin Genet. 2014;7:169–75.PubMedPubMedCentral
15.
Eggermann T, Binder G, Brioude F, Maher ER, Lapunzina P, Cubellis MV, et al. CDKN1C mutations: two sides of the same coin. Trend Mol Med. 2014;20(11):614–22.CrossRef
16.
Romanelli V, Belinchón A, Benito-Sanz S, Martínez-Glez V, Gracia-Bouthelier R, Heath KE, et al. CDKN1C (p57(Kip2)) analysis in Beckwith-Wiedemann syndrome (BWS) patients: genotype-phenotype correlations, novel mutations, and polymorphisms. Am J Med Genet. 2010;152A:1390–7.PubMed
17.
Russo S, Calzari L, Mussa A, Mainini E, Cassina M, Di Candia S, et al. A multi-method approach to the molecular diagnosis of overt and borderline 11p15.5 defects underlying Silver-Russell and Beckwith-Wiedemann sindromes. Clinical. Epigenetics. 2016;8:23.CrossRef
18.
Mussa A, Russo S, Larizza L, Riccio A, Ferrero GB, et al. (Epi)genotype-phenotype correlations in Beckwith-Wiedemann syndrome. Eur J Hum Genet. 2016;24:183–90.CrossRefPubMed
19.
Li M, Squire J, Shuman C, Fei YL. Imprinting status of 11p15 genes in Beckwith Wiedemann syndrome patients with CDKN1C mutations. Genomics. 2001;74:3.
20.
Cooper WN, Luharia A, Evans GA, Raza H, Haire AC, Grundy R, et al. Molecular subtypes and phenotypic expression of Beckwith Wiedemann syndrome syndrome. Eur J Hum Genet. 2005;13:10.CrossRef
21.
Grati FR, Turolla L, D'Ajello P, Ruggeri A, Miozzo M, Bracalente G, et al. Chromosome 11 segmental paternal isodisomy in amniocytes from two fetuses with omphalocoele: new highlights on phenotype-genotype correlations in Beckwith-Wiedemann syndrome. J Med Genet. 2007;44(4):257–63.CrossRefPubMedPubMedCentral
22.
Radhakrishna U, Nath SK, McElreavey K, Ratnamala U, Sun C, Maiti AK, et al. Genome-wide linkage and copy number variation analysis reveals 710 kb duplication on chromosome 1p31.3 responsible for autosomal dominant omphalocele. J Med Genet. 2012;49(4):270–6.CrossRefPubMedPubMedCentral
23.
Kanagawa SL, Begleiter ML, Ostlie DJ, Holcomb G, Drake W, Butler MG. Omphalocele in three generations with autosomal dominant transmission. J Med Genet. 2002;39:184–5.CrossRefPubMedPubMedCentral
24.
Feldkamp ML, Srisukhumbowornchai S, Romitti PA, Olney RS, Richardson SD, Botto LD. Self-reported maternal cigarette smoke exposure during the periconceptional period and the risk for omphalocoele. Paediatr Perinat Epidemiol. 2014;28(1):67–73.CrossRefPubMed
25.
Pryde PG, Greb A, Isada NB, Johnson MB, Klein M, Evans MI. Familial omphalocele: considerations in genetic counseling. Am J Med Genet. 1992;44:624–7.CrossRefPubMed
26.
Van Eijck FC, Hoogeveen YL, van Weel C, Rieu PN, Wijnen RM. Minor and giant omphalocele: long-term outcomes and quality of life. J Pediatr Surg. 2009;44(7):1355–9.CrossRefPubMed
27.
Garne E. Atrial and ventricular septal defects - epidemiology and spontaneous closure. J Matern Fetal Neonatal Med. 2006;19(5):271–6.CrossRefPubMed
28.
Tabano S, Colapietro P, Cetin I, Grati FR, Zanutto S, Mandò C, et al. Epigenetic modulation of the IGF2/H19 imprinted domain in human embryonic and extra-embryonic compartments and its possible role in fetal growth restriction. Epigenetics. 2010;5(4):313–24.CrossRefPubMed
29.
Calvello M, Tabano S, Colapietro P, Maitz S, Pansa A, Augello C, et al. Quantitative DNA methylation analysis improves epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome. Epigenetics. 2013;8(10):1053–60.CrossRefPubMedPubMedCentral
30.
Paganini L, Carlessi N, Fontana L, Silipigni R, Motta S, Fiori S, et al. Beckwith-Wiedemann syndrome prenatal diagnosis by methylation analysis in chorionic villi. Epigenetics. 2015;10(7):643–9.CrossRefPubMedPubMedCentral
31.
Arboleda VA, Lee H, Parnaik R, Fleming A, Banerjee A, Ferraz-de-Souza B, et al. Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome. Nat Genet. 2012;44(7):788–92.CrossRefPubMedPubMedCentral
Metadata
Title
Sequence variants identification at the KCNQ1OT1:TSS differentially Methylated region in isolated omphalocele cases
Authors
Maria Francesca Bedeschi
Mariarosaria Calvello
Leda Paganini
Lidia Pezzani
Marco Baccarin
Laura Fontana
Silvia M. Sirchia
Silvana Guerneri
Lorena Canazza
Ernesto Leva
Lorenzo Colombo
Faustina Lalatta
Fabio Mosca
Silvia Tabano
Monica Miozzo
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2017
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-017-0470-z

Other articles of this Issue 1/2017

BMC Medical Genetics 1/2017 Go to the issue

Research article

Clinical and molecular genetic characterization of familial MECP2 duplication syndrome in a Chinese family

Research article

The gene–treatment interaction of paraoxonase-1 gene polymorphism and statin therapy on insulin secretion in Japanese patients with type 2 diabetes: Fukuoka diabetes registry

Research article

Vitamin D receptor gene polymorphisms in association with diabetic nephropathy: a systematic review and meta-analysis

Research article

Exploring digenic inheritance in arrhythmogenic cardiomyopathy

Case report

Living kidney transplantation between brothers with unrecognized renal amyloidosis as the first manifestation of familial Mediterranean fever: a case report

Research article

DNA methylation profiles of elderly individuals subjected to indentured childhood labor and trauma