Wang Yefeng, Wu Xinghan, Zhao Sha, Xu Ningan
Department of Cardiology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha, Hunan, China.
Medical Genetics Department, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha, Hunan, China.
Front Genet. 2025 Jul 2;16:1588657. doi: 10.3389/fgene.2025.1588657. eCollection 2025.
Rubinstein-Taybi syndrome is an extremely rare autosomal dominant genetic disease. The incidence of RSTS ranges from 1/100 000 to 125 000.
We retrospectively reviewed the phenotype and genotype of two children who were diagnosed with RSTS in Hunan Province Children's Hospital from January 2022 to December 2023. Clinical data of the children were collected. Whole-exome sequencing was performed on the children. The candidate variants were verified by Sanger sequencing in the pedigree, followed by pathogenicity analysis.
The main clinical presentations of the two cases were growth retardation, special facial features, and mild intellectual disability. Three mutations were detected by exome sequencing, all of which were sporadic mutations verified by Sanger sequencing. In case 1, pathological mutations were detected in gene and gene. A heterozygous mutation c. 3934C>T (p. Arg1312Ter) was detected in exon 24 of EP300 gene. A heterozygous mutation c. 5843G>A (p. Arg1948 His) was detected in exon 18 of NSD1 gene. In case 2, a heterozygous mutation (c.2749C>T) (p. Gln917 *) was detected in exon 14 of gene, which has not been reported in the literature so far. According to ACMG guidelines, this mutation was preliminarily determined to be pathogenic. Comparative analysis of phenotypic differences between the Chinese cohort and the Cohen JL and Fergelot P. cohorts revealed that arched eyebrows, downslanting palpebral fissures, and low-set ears were significantly more common in the Chinese population.
gene c.2749C>T heterozygous mutation may be the genetic cause of Rubinstein Taybi syndrome. gene combined with gene mutation may lead to atypical clinical presentations. These findings further enrich the variation spectrum of gene.
鲁宾斯坦-泰比综合征是一种极其罕见的常染色体显性遗传病。鲁宾斯坦-泰比综合征的发病率在1/100000至1/125000之间。
我们回顾性分析了2022年1月至2023年12月在湖南省儿童医院确诊为鲁宾斯坦-泰比综合征的两名儿童的表型和基因型。收集了这些儿童的临床资料。对这些儿童进行了全外显子组测序。通过桑格测序在家族中验证候选变异，随后进行致病性分析。
两例患者的主要临床表现为生长发育迟缓、特殊面容和轻度智力障碍。外显子组测序检测到三个突变，均为经桑格测序验证的散发性突变。病例1中，在 基因和 基因中检测到病理性突变。在EP300基因第24外显子中检测到杂合突变c.3934C>T（p.Arg1312Ter）。在NSD1基因第18外显子中检测到杂合突变c.5843G>A（p.Arg1948His）。病例2中，在 基因第14外显子中检测到杂合突变（c.2749C>T）（p.Gln917*），该突变迄今未见文献报道。根据美国医学遗传学与基因组学学会（ACMG）指南，初步判定该突变具有致病性。中国队列与Cohen JL和Fergelot P.队列的表型差异比较分析显示，在中国人群中，挑眉、睑裂下斜和低位耳更为常见。
基因c.2749C>T杂合突变可能是鲁宾斯坦-泰比综合征的遗传病因。 基因与 基因突变可能导致非典型临床表现。这些发现进一步丰富了鲁宾斯坦-泰比综合征的变异谱。
