Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Child Neurology, Toyota Municipal Child Development Center Nozomi Clinic, Toyota, Japan.
J Hum Genet. 2023 Feb;68(2):87-90. doi: 10.1038/s10038-022-01088-z. Epub 2022 Oct 13.
Angelman syndrome (AS) is caused by the functional absence of the maternal ubiquitin-protein ligase E3A (UBE3A) gene. Approximately 5% of AS is caused by paternal uniparental disomy of chromosome 15 (UPD(15)pat), most of which is considered to result from monosomy rescue. However, little attention has focused on how UPD(15)pat occurs. We suggest the mitotic nondisjunction mechanism as a cause of UPD(15)pat in a six-year-old patient presenting with distinctive characteristics in line with AS. DNA methylation screening of 15q11-q13 showed a paternal band and a faint maternal band, suggestive of mosaic status. By trio-based microsatellite analysis, we confirmed a large proportion of UPD(15)pat cells and a small proportion of cells of biparental origin. Single nucleotide polymorphism (SNP) microarray revealed isodisomy of the entire chromosome 15. These results suggest that the UPD(15)pat of the patient resulted from mitotic nondisjunction, which may also be the cause of other cases of AS with UPD(15)pat.
天使综合征（AS）是由母源泛素蛋白连接酶 E3A（UBE3A）基因功能缺失引起的。约 5%的 AS 由 15 号染色体（15q）父源单亲二体性（UPD(15)pat）引起，其中大多数被认为是由于单体挽救所致。然而，人们对 UPD(15)pat 的发生机制关注甚少。我们提出有丝分裂不分离机制可能是导致一名 6 岁患儿出现 AS 典型特征的 UPD(15)pat 的原因。15q11-q13 的 DNA 甲基化筛查显示存在一条父源带和一条微弱的母源带，提示为嵌合体状态。通过基于三亲的微卫星分析，我们证实了存在大量 UPD(15)pat 细胞和少量双亲源性细胞。单核苷酸多态性（SNP）微阵列显示整个 15 号染色体的同二倍性。这些结果提示该患者的 UPD(15)pat 是由有丝分裂不分离引起的，这也可能是其他 UPD(15)pat 型 AS 病例的原因。
