A novel IGF2/H19 domain triplication in the 11p15.5 imprinting region causing either Beckwith-Wiedemann or Silver-Russell syndrome in a single family.
Defects of 11p15.5 imprinting result in two growth disorders with opposite phenotypes: Beckwith-Wiedemann syndrome (BWS) characterized by overgrowth and Silver-Russell syndrome (SRS) associated with growth retardation. In a small group of patients with BWS and SRS, copy number variations (CNVs) involving the 11p15.5 region are observed; and their effects depend on the localization, size, and the parental mode of transmission. We report a novel IGF2/H19 domain cis-triplication in the 11p15.5 region identified in a girl with BWS and her father with symptoms of SRS. To the best of our knowledge, this is the first report of IGF2/H19 domain triplication associated with BWS or SRS and the second report of an additional copy of this region in an individual with clinical features of SRS. This study shows that paternal IGF2/H19 domain triplication results in BWS, gives additional support to the hypothesis that the maternal amplification of IGF2/H19 domain may lead to the manifestation of SRS and underlines difficulties of genetic counseling in patients with CNVs involving the 11p15.5 region. © 2016 Wiley Periodicals, Inc.
Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland.
Dorota
D
Jurkiewicz
Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland.|Department of Child and Adolescent Psychiatry, Medical University of Warsaw, Warsaw, Poland.
Monika
M
Kugaudo
Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland.|Department of Pediatrics, Medical University of Warsaw, Warsaw, Poland.
Agata
A
Skórka
Department of Pediatrics, Wroclaw Medical University, Wroclaw, Poland.
Robert
R
Śmigiel
Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
Marta
M
Smyk
Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland.
Elżbieta
E
Ciara
Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland.
Krystyna
K
Chrzanowska
Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland.
Małgorzata
M
Krajewska-Walasek
D001506:Beckwith-Wiedemann Syndrome / Q000175:diagnosis* / Q000235:genetics*; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D005260:Female; D005784:Gene Amplification; D056726:Genetic Association Studies; D018392:Genomic Imprinting; D006801:Humans; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008957:Models, Genetic; D010375:Pedigree; D010641:Phenotype; D062085:RNA, Long Noncoding / Q000235:genetics*; D056730:Silver-Russell Syndrome / Q000175:diagnosis* / Q000235:genetics*
C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D007335:Insulin-Like Growth Factor II
11p15.5 imprinting region; Beckwith-Wiedemann syndrome; IGF2/H19 domain triplication; Silver-Russell syndrome