Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
Department of Pediatrics, Hokkaido University of Medical, Sapporo, Japan.
J Med Genet. 2018 Aug;55(8):567-570. doi: 10.1136/jmedgenet-2017-104986. Epub 2018 Feb 17.
Paternal uniparental disomy for chromosome 7 (upd(7)pat) is extremely rare, and only four cases have been previously reported. As these cases were accompanied by autosomal-recessive disorders which are likely to be involved in growth restriction, the relevance of upd(7)pat to the overgrowth phenotype remains unclear. Here we describe one case of upd(7)pat with no additional genetic diseases, which may answer the question.
A 5-year-old Japanese boy presented with a tall stature of unknown causes. To detect the genetic cause of the tall stature, we performed Sanger sequencing, targeted resequencing, comparative genomic hybridisation and single-nucleotide polymorphism (SNP) array analyses, methylation analysis and microsatellite analysis.
We could not detect pathogenic variants in causative genes for overgrowth syndrome or apparent copy number alterations. DNA methylation analysis revealed hypomethylation at the , and differentially methylated regions. SNP array and microsatellite analyses suggested paternal uniparental isodisomy for chromosome 7. Furthermore, we could not identify homozygous mutations of known causative genes for inherited disorders on chromosome 7.
We report the first case of upd(7)pat with an overgrowth phenotype.
7 号染色体单亲二体性（upd(7)pat）极为罕见，此前仅报道过 4 例。由于这些病例伴有常染色体隐性疾病，这些疾病可能与生长受限有关，因此 upd(7)pat 与过度生长表型的相关性尚不清楚。在这里，我们描述了一例 upd(7)pat 病例，该病例无其他遗传疾病，这可能解答了这个问题。
一名 5 岁的日本男孩因不明原因的身材高大就诊。为了检测身材高大的遗传原因，我们进行了 Sanger 测序、靶向重测序、比较基因组杂交和单核苷酸多态性 (SNP) 芯片分析、甲基化分析和微卫星分析。
我们未在导致过度生长综合征的致病基因或明显的拷贝数改变中检测到致病性变异。DNA 甲基化分析显示 、 和 差异甲基化区域的低甲基化。SNP 芯片和微卫星分析提示 7 号染色体单亲二体性。此外，我们未能在 7 号染色体上发现已知遗传性疾病的致病基因的纯合突变。
我们报告了首例伴有过度生长表型的 upd(7)pat 病例。
