Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, No. 59, Xiangzhu Road, Nanning, China.
Department of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
BMC Med Genomics. 2024 Apr 20;17(1):95. doi: 10.1186/s12920-024-01883-x.
NSUN2-intellectual disability syndrome, also known as intellectual disability type 5 (MRT5), is an autosomal recessive disorder that is characterized by intellectual disability (ID), postnatal growth retardation, dysmorphic facies, microcephaly, short stature, developmental delay, language impairment and other congenital abnormalities. The disease is caused by mutations in the NSUN2 gene, which encodes a tRNA cytosine methyltransferase that has an important role in spindle assembly during mitosis and chromosome segregation. In this study, we recruited a family that had two individuals with ID. Whole exome sequencing was performed to identify a homozygous frameshift variant (c.1171_1175delACCAT(p.Thr391fs18)) in NSUN2 (NM_017755.5) in the proband. The varint was confirmed as segregating in his affected brother and his parents by Sanger sequencing. The individuals that we described showed a similar dysmorphology profile to that associated with MRT5. To analyze the correlations between genotypes of NSUN2 and phenotypes of individuals with ID, we examined 17 variants and the associated phenotypes from 32 ID individuals in current and previous studies. We concluded that mutations in NSUN2 cause a wide range of phenotypic defects. Although some clinical manifestations were highly variable, the core phenotypes associated with NSUN2 mutations were dysmorphic facies, microcephaly, short stature, ID, growth restriction, language impairment, hypotonia and delayed puberty. Our study expands the genetic spectrum of NSUN2 mutations and helps to further define the genotype-phenotype correlations in MRT5.
NSUN2-智力残疾综合征，也称为智力残疾 5 型（MRT5），是一种常染色体隐性遗传病，其特征为智力残疾（ID）、出生后生长迟缓、发育异常面容、小头畸形、身材矮小、发育迟缓、语言障碍和其他先天性异常。该疾病由 NSUN2 基因突变引起，该基因编码一种 tRNA 胞嘧啶甲基转移酶，在有丝分裂过程中的纺锤体组装和染色体分离中具有重要作用。在这项研究中，我们招募了一个有两个 ID 患者的家庭。对先证者进行全外显子组测序，以鉴定 NSUN2 基因（NM_017755.5）中的纯合移码变异（c.1171_1175delACCAT[p.Thr391fs18]）。通过 Sanger 测序证实该变异在其受影响的兄弟及其父母中存在共分离。我们描述的个体表现出与 MRT5 相关的相似发育异常表型。为了分析 NSUN2 基因型与 ID 个体表型之间的相关性，我们检查了来自当前和以前研究的 32 个 ID 个体的 17 个变体及其相关表型。我们得出结论，NSUN2 突变导致广泛的表型缺陷。尽管一些临床表现高度可变，但与 NSUN2 突变相关的核心表型是发育异常面容、小头畸形、身材矮小、ID、生长受限、语言障碍、低张力和青春期延迟。我们的研究扩展了 NSUN2 突变的遗传谱，并有助于进一步定义 MRT5 中的基因型-表型相关性。
