PDF(Pubmed)
Abstract：
BACKGROUND: Okur-Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual disability, developmental delay, and multisystemic abnormalities.
METHODS: We performed the whole-exome sequencing for a patient in a Chinese family. The co-segregation study using the Sanger sequencing method was performed among family members. Reverse transcription and quantitative real-time polymerase chain reaction were carried out using total RNA from blood samples of the proband and wild-type control subjects. A review of patients with OCNDS harboring CSNK2A1 pathogenic variants was conducted through a comprehensive search of the PubMed database.
RESULTS: We identified a novel CSNK2A1 frameshift variant p.Tyr323Leufs*16 in a Chinese family. The proband, a 31-year-old female, presented with abnormal eating habits, recurrent seizures, language impairment, and intellectual disability. Her mother exhibited postnatal hernias, splenomegaly, and a predisposition to infections, but showed no significant developmental impairments or intellectual disability. Genetic studies revealed the presence of this variant in CSNK2A1 in both the proband and her mother. Transcription analysis revealed this variant may lead to nonsense-mediated mRNA decay, suggesting haploinsufficiency as a potential disease mechanism. We reviewed 47 previously reported OCNDS cases and discovered that individuals carrying CSNK2A1 null variants may exhibit a diminished frequency of symptoms linked to language deficits, dysmorphic facial features, or intellectual disability, consequently presenting an overall milder phenotype when compared to those with missense variants.
CONCLUSIONS: We report a novel frameshift variant, p.Tyr323Leufs*16, in an OCNDS family with a generally mild phenotype. This study may broaden the spectrum of clinical presentations associated with OCNDS and contribute novel insights into the genotype-phenotype correlation of this condition.
METHODS: We performed the whole-exome sequencing for a patient in a Chinese family. The co-segregation study using the Sanger sequencing method was performed among family members. Reverse transcription and quantitative real-time polymerase chain reaction were carried out using total RNA from blood samples of the proband and wild-type control subjects. A review of patients with OCNDS harboring CSNK2A1 pathogenic variants was conducted through a comprehensive search of the PubMed database.
RESULTS: We identified a novel CSNK2A1 frameshift variant p.Tyr323Leufs*16 in a Chinese family. The proband, a 31-year-old female, presented with abnormal eating habits, recurrent seizures, language impairment, and intellectual disability. Her mother exhibited postnatal hernias, splenomegaly, and a predisposition to infections, but showed no significant developmental impairments or intellectual disability. Genetic studies revealed the presence of this variant in CSNK2A1 in both the proband and her mother. Transcription analysis revealed this variant may lead to nonsense-mediated mRNA decay, suggesting haploinsufficiency as a potential disease mechanism. We reviewed 47 previously reported OCNDS cases and discovered that individuals carrying CSNK2A1 null variants may exhibit a diminished frequency of symptoms linked to language deficits, dysmorphic facial features, or intellectual disability, consequently presenting an overall milder phenotype when compared to those with missense variants.
CONCLUSIONS: We report a novel frameshift variant, p.Tyr323Leufs*16, in an OCNDS family with a generally mild phenotype. This study may broaden the spectrum of clinical presentations associated with OCNDS and contribute novel insights into the genotype-phenotype correlation of this condition.
摘要：
背景：Okur-Chung神经发育综合征（OCNDS）是一种由CSNK2A1致病变异引起的罕见常染色体显性疾病。它的特点是智力残疾，发育迟缓,和多系统异常。
方法：我们对一个中国家庭的患者进行了全外显子组测序。使用Sanger测序方法的共分离研究在家庭成员之间进行。使用来自先证者和野生型对照受试者的血液样品的总RNA进行逆转录和定量实时聚合酶链反应。通过对PubMed数据库的全面搜索，对携带CSNK2A1致病性变异的OCNDS患者进行了综述。
结果：我们在一个中国家族中鉴定出一种新型CSNK2A1移码变种p.Tyr323Leufs*16。先证者，一个31岁的女性,有异常的饮食习惯，反复发作,语言障碍，智力残疾。她的母亲表现出产后疝气，脾肿大,和感染的易感性，但没有明显的发育障碍或智力障碍。遗传研究表明，先证者和她的母亲在CSNK2A1中都存在这种变体。转录分析显示此变体可能导致无义介导的mRNA衰减，提示单倍体功能不全是一种潜在的疾病机制。我们回顾了先前报道的47例OCNDS病例，发现携带CSNK2A1无效变异的个体可能表现出与语言缺陷相关的症状频率降低。畸形面部特征，或者智力残疾，因此，与具有错义变体的表型相比，呈现出总体较温和的表型。
结论：我们报告了一种新的移码变体，p.Tyr323Leufs*16，在OCNDS家族中，表型一般为轻度。这项研究可能会拓宽与OCNDS相关的临床表现的范围，并为这种情况的基因型-表型相关性提供新的见解。
方法：我们对一个中国家庭的患者进行了全外显子组测序。使用Sanger测序方法的共分离研究在家庭成员之间进行。使用来自先证者和野生型对照受试者的血液样品的总RNA进行逆转录和定量实时聚合酶链反应。通过对PubMed数据库的全面搜索，对携带CSNK2A1致病性变异的OCNDS患者进行了综述。
结果：我们在一个中国家族中鉴定出一种新型CSNK2A1移码变种p.Tyr323Leufs*16。先证者，一个31岁的女性,有异常的饮食习惯，反复发作,语言障碍，智力残疾。她的母亲表现出产后疝气，脾肿大,和感染的易感性，但没有明显的发育障碍或智力障碍。遗传研究表明，先证者和她的母亲在CSNK2A1中都存在这种变体。转录分析显示此变体可能导致无义介导的mRNA衰减，提示单倍体功能不全是一种潜在的疾病机制。我们回顾了先前报道的47例OCNDS病例，发现携带CSNK2A1无效变异的个体可能表现出与语言缺陷相关的症状频率降低。畸形面部特征，或者智力残疾，因此，与具有错义变体的表型相比，呈现出总体较温和的表型。
结论：我们报告了一种新的移码变体，p.Tyr323Leufs*16，在OCNDS家族中，表型一般为轻度。这项研究可能会拓宽与OCNDS相关的临床表现的范围，并为这种情况的基因型-表型相关性提供新的见解。
