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

BMC Medical Genetics

Marco Baccarin¹  Silvia M. Sirchia¹  Ernesto Leva¹  Leda Paganini¹  Maria Francesca Bedeschi²  Lorenzo Colombo³  Silvia Tabano⁴  Fabio Mosca⁴  Lidia Pezzani⁵  Laura Fontana⁵  Lorena Canazza⁵  Mariarosaria Calvello⁵  Silvana Guerneri⁶  Faustina Lalatta⁶  Monica Miozzo⁷ 

[1] Department of Pathophysiology & Transplantation, Università degli Studi di Milano;Clinical Genetics Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico;Department of Health Science, Università degli Studi di Milano;Department of Pediatric Surgery, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico;Division of Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico;Medical Genetics Laboratory, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico;Neonatal Intensive Care Unit, Department of Clinical Science and Community Health, Università degli Studi di Milano and Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico;

关键词: Abdominal wall defects;    Beckwith-Wiedemann syndrome;    CDKN1C;    Genomic imprinting;    KCNQ1OT1:TSS-DMR;    Omphalocele;   

DOI  :  10.1186/s12881-017-0470-z

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown