title: Microduplication of the ICR2 domain at chromosome 11p15 and familial Silver-Russell syndrome.
abstract: Silver-Russell syndrome (SRS) is characterized by severe intrauterine and postnatal growth retardation in association with a typical small triangular face and other variable features. Genetic and epigenetic disturbances are detected in about 50% of the patients. Most frequently, SRS is caused by altered gene expression on chromosome 11p15 due to hypomethylation of the telomeric imprinting center (ICR1) that is present in at least 40% of the patients. Maternally inherited duplications encompassing ICR1 and ICR2 domains at 11p15 were found in a few patients, and a microduplication restricted to ICR2 was described in a single SRS child. We report on a microduplication of the ICR2 domain encompassing the KCNQ1, KCNQ1OT1, and CDKN1C genes in a three-generation family: there were four instances of paternal transmissions of the microduplication from a single male uniformly resulting in normal offspring, and five maternal transmissions, via two clinically normal sisters, with all the children exhibiting SRS. This report provides confirmatory evidence that a microduplication restricted to the ICR2 domain results in SRS when maternally transmitted.
authors: Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, Brazil.
authors: Adriano
authors: A
authors: Bonaldi
authors: Juliana F
authors: JF
authors: Mazzeu
authors: Silvia S
authors: SS
authors: Costa
authors: Rachel S
authors: RS
authors: Honjo
authors: Débora R
authors: DR
authors: Bertola
authors: Lilian M J
authors: LM
authors: Albano
authors: Isabel M
authors: IM
authors: Furquim
authors: Chong A
authors: CA
authors: Kim
authors: Angela M
authors: AM
authors: Vianna-Morgante
mesh_terms: D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D020440:Gene Duplication / Q000235:genetics*; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008297:Male; D010375:Pedigree; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D056730:Silver-Russell Syndrome / Q000235:genetics* / Q000473:pathology*; D016615:Telomere / Q000235:genetics*
chemical_list: C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C485621:KCNQ1OT1 long non-coding RNA, human; D024642:Potassium Channels, Voltage-Gated