De novo IGF2 mutation on the paternal allele in a patient with Silver-Russell syndrome and ectrodactyly
De novo IGF2 mutation on the paternal allele in a patient with Silver-Russell syndrome and ectrodactyly
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DOI：
10.1002/humu.23253
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发表时间：
2017-08-01
期刊：
影响因子：
3.9
通讯作者：
Ogata, Tsutomu
中科院分区：
文献类型：
--
作者：
Yamoto, Kaori;Saitsu, Hirotomo;Ogata, Tsutomu
虽然已知父亲表达的IGF 2在胎盘和身体生长中起关键作用，但在IGF 2中仅发现单一突变。我们通过全外显子组测序鉴定了导致移码的从头IGF 2插入缺失突变（NM_000612.5：c.110_117delinsAGGTAA，p.（Leu 37 Glnfs *31）），在一名患者的银罗素综合征，缺指，男性化不足的生殖器，发育迟缓，胎盘发育不全。此外，我们证明了突变驻留在父亲的等位基因通过测序的长PCR产物窝藏突变和甲基化敏感的SmaI和Sal I位点之前和之后SmaI/Sal I消化。这些结果，连同先前在来自一个父系遗传的IGF 2无义突变家族的4例病例中的发现，以及在可变H19差异甲基化区域表型突变导致IGF 2表达受损的患者中的发现，表明该患者的整个表型可由IGF 2突变解释，并且表型严重程度主要由靶组织中的IGF 2表达水平决定。
Although paternally expressed IGF2 is known to play a critical role in placental and body growth, only a single mutation has been found in IGF2. We identified, through whole-exome sequencing, a de novo IGF2 indel mutation leading to frameshift (NM_000612.5:c.110_117delinsAGGTAA, p.(Leu37Glnfs*31)) in a patient with Silver-Russell syndrome, ectrodactyly, undermasculinized genitalia, developmental delay, and placental hypoplasia. Furthermore, we demonstrated that the mutation resided on the paternal allele by sequencing the long PCR product harboring the mutation- and methylation-sensitive SmaI and SalI sites before and after SmaI/SalI digestion. The results, together with the previous findings in four cases from a single family with a paternally inherited IGF2 nonsense mutation and those in patients with variable H19 differentially methylated region epimutations leading to compromised IGF2 expression, suggest that the whole phenotype of this patient is explainable by the IGF2 mutation, and that phenotypic severity is primarily determined by the IGF2 expression level in target tissues.