Soma Noriko, Higashimoto Ken, Imamura Masaru, Saitoh Akihiko, Soejima Hidenobu, Nagasaki Keisuke
Department of Homeostatic Regulation and Development, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Faculty of Medicine, Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Saga University, Saga, Japan.
Am J Med Genet A. 2017 Apr;173(4):1077-1081. doi: 10.1002/ajmg.a.38111.
Perlman syndrome is a rare overgrowth syndrome characterized by polyhydramnios, macrosomia, distinctive facial appearance, renal dysplasia, and a predisposition to Wilms' tumor. The syndrome is often associated with a high neonatal mortality rate and there are few reports of long-term survivors. We studied a 6-year-old Japanese female patient, who was diagnosed with Perlman syndrome, with novel compound heterozygous mutations in DIS3L2 (c.[367-2A > G];[1328T > A]), who has survived long term. Most reported DIS3L2 mutations have been the homozygous deletion of exon 6 or exon 9, and these mutations would certainly have caused the loss of both RNA binding and degradation activity. We have identified new compound heterozygous mutations in the DIS3L2 of this long-term survivor of Perlman syndrome. The reason our patient has survived long-term would be a missense mutation (c.1328 T > A, p.Met443Lys) having retained RNA binding in both the cold-shock domains and the S1 domain, and through partial RNA degradation. If partial exonuclease functions remain in at least one allele, long-term survival may be possible. Further studies of Perlman syndrome patients with proven DIS3L2 mutations are needed to clarify genotype-phenotype correlation.
佩尔曼综合征是一种罕见的过度生长综合征，其特征为羊水过多、巨大儿、独特的面部外观、肾发育不良以及患威尔姆斯瘤的倾向。该综合征常与高新生儿死亡率相关，长期存活者的报道很少。我们研究了一名6岁的日本女性患者，她被诊断为佩尔曼综合征，携带DIS3L2基因的新型复合杂合突变（c.[367-2A＞G]；[1328T＞A]），并长期存活。大多数报道的DIS3L2突变是外显子6或外显子9的纯合缺失，这些突变肯定会导致RNA结合和降解活性丧失。我们在这名佩尔曼综合征的长期存活者的DIS3L2基因中鉴定出了新的复合杂合突变。我们的患者能够长期存活的原因可能是一个错义突变（c.1328 T＞A，p.Met443Lys）在冷休克结构域和S1结构域中都保留了RNA结合能力，并通过部分RNA降解实现。如果至少一个等位基因中仍保留部分核酸外切酶功能，就有可能实现长期存活。需要对已证实携带DIS3L2突变的佩尔曼综合征患者进行进一步研究，以阐明基因型与表型的相关性。
