Division of Pediatric Genetics, Metabolism and Genomic Medicine, University of Michigan Medical School, Detroit, MI, USA.
Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
J Hum Genet. 2021 Apr;66(4):439-443. doi: 10.1038/s10038-020-00858-x. Epub 2020 Oct 16.
Kagami-Ogata syndrome (KOS14) is a rare imprinting disorder characterized by a unique constellation of phenotypes including bell-shaped small thorax with coat-hanger appearance of the ribs. We encountered an African American female infant with KOS14 phenotype and 46,XX,t(2;14)(q11.2;q32.2)mat. After excluding upd(14)pat and an epimutation (hypermethylation) and a deletion affecting the maternally derived 14q32.2 imprinted region, we performed whole-genome sequencing, revealing that the translocation was generated between noncoding region at 2q11.2 and intron 6 of MEG3 at 14q32.2. Subsequent Sanger sequencing for the fusion points showed that the chromosomal fusion on the der(2) chromosome occurred between Chr2:102,193,994 (bp) and Chr14:101,314,628 (bp) in association with an insertion of 5-bp segment of unknown origin and that on the der(14) chromosome took place between Chr14:101,314,627 (bp) and Chr2:102,193,995 (bp) in association with an insertion of 1-bp segment of unknown origin (according to GRCh37/hg19). The results, together with the previous data in patients with KOS14, imply that the MEG3 disruption by 46,XX,t(2;14)(q11.2;q32.2)mat caused silencing of all MEGs including RTL1as and resultant excessive RTL1 expression, leading to the development of KOS14. To our knowledge, while Robertsonian translocations involving chromosome 14 have been reported in KOS14, this is the first case of KOS14 caused by a chromosomal translocation involving the 14q32.2 imprinted region.
Kagami-Ogata 综合征（KOS14）是一种罕见的印迹障碍，其特征是具有独特的表型组合，包括钟形小胸和肋骨呈衣架状。我们遇到了一名非洲裔美国女婴，具有 KOS14 表型和 46,XX,t(2;14)(q11.2;q32.2)mat。在排除 upd(14)pat 和一个印迹异常（高甲基化）以及影响母系 14q32.2 印迹区域的缺失后，我们进行了全基因组测序，结果显示易位是在 2q11.2 的非编码区域和 14q32.2 的 MEG3 内含子 6 之间产生的。随后对融合点进行 Sanger 测序显示，在 der(2)染色体上，染色体融合发生在 Chr2:102,193,994（bp）和 Chr14:101,314,628（bp）之间，伴有一个起源不明的 5-bp 片段的插入，而在 der(14)染色体上，融合发生在 Chr14:101,314,627（bp）和 Chr2:102,193,995（bp）之间，伴有一个起源不明的 1-bp 片段的插入（根据 GRCh37/hg19）。这些结果与 KOS14 患者的先前数据一起表明，46,XX,t(2;14)(q11.2;q32.2)mat 导致 MEG3 的破坏，从而使包括 RTL1as 在内的所有 MEGs 沉默，并导致 RTL1 表达过度，导致 KOS14 的发生。据我们所知，虽然 14 号染色体的罗伯逊易位已在 KOS14 中报道，但这是首例由涉及 14q32.2 印迹区域的染色体易位引起的 KOS14 病例。
