Abstract：
BACKGROUND: Lowe syndrome is characterized by the presence of congenital cataracts, psychomotor retardation, and dysfunctional proximal renal tubules. This study presents a case of an atypical phenotype, investigates the genetic characteristics of eight children diagnosed with Lowe syndrome in southern China, and performs functional analysis of the novel variants.
METHODS: Whole-exome sequencing was conducted on eight individuals diagnosed with Lowe syndrome from three medical institutions in southern China. Retrospective collection and analysis of clinical and genetic data were performed, and functional analysis was conducted on the five novel variants.
RESULTS: In our cohort, the clinical symptoms of the eight Lowe syndrome individuals varied. One patient was diagnosed with Lowe syndrome but did not present with congenital cataracts. Common features among all patients included cognitive impairment, short stature, and low molecular weight proteinuria. Eight variations in the OCRL gene were identified, encompassing three previously reported and five novel variations. Among the novel variations, three nonsense mutations were determined to be pathogenic, and two patients harboring novel missense variations of uncertain significance exhibited severe typical phenotypes. Furthermore, all novel variants were associated with altered protein expression levels and impacted primary cilia formation.
CONCLUSIONS: This study describes the first case of an atypical Lowe syndrome patient without congenital cataracts in China and performs a functional analysis of novel variants in the OCRL gene, thereby expanding the understanding of the clinical manifestations and genetic diversity associated with Lowe syndrome.
METHODS: Whole-exome sequencing was conducted on eight individuals diagnosed with Lowe syndrome from three medical institutions in southern China. Retrospective collection and analysis of clinical and genetic data were performed, and functional analysis was conducted on the five novel variants.
RESULTS: In our cohort, the clinical symptoms of the eight Lowe syndrome individuals varied. One patient was diagnosed with Lowe syndrome but did not present with congenital cataracts. Common features among all patients included cognitive impairment, short stature, and low molecular weight proteinuria. Eight variations in the OCRL gene were identified, encompassing three previously reported and five novel variations. Among the novel variations, three nonsense mutations were determined to be pathogenic, and two patients harboring novel missense variations of uncertain significance exhibited severe typical phenotypes. Furthermore, all novel variants were associated with altered protein expression levels and impacted primary cilia formation.
CONCLUSIONS: This study describes the first case of an atypical Lowe syndrome patient without congenital cataracts in China and performs a functional analysis of novel variants in the OCRL gene, thereby expanding the understanding of the clinical manifestations and genetic diversity associated with Lowe syndrome.
摘要：
背景：Lowe综合征的特征是先天性白内障，精神运动性迟钝,和功能失调的近端肾小管。这项研究提出了一个非典型表型的案例，调查中国南方8例Lowe综合征患儿的遗传特征,并对新变体进行功能分析。
方法：对来自中国南方三家医疗机构的8例Lowe综合征患者进行全外显子组测序。回顾性收集和分析临床和遗传数据，并对5个新的变异体进行了功能分析。
结果：在我们的队列中，八个Lowe综合征个体的临床症状各不相同。一名患者被诊断患有Lowe综合征，但未出现先天性白内障。所有患者的共同特征包括认知障碍，身材矮小,和低分子量蛋白尿。鉴定了OCRL基因的八个变异，包括三个以前报道的和五个新的变化。在小说中，三个无义突变被确定为致病性，两名具有不确定意义的新型错义变异的患者表现出严重的典型表型。此外，所有新变异均与蛋白表达水平改变相关,并影响初级纤毛形成.
结论：这项研究描述了中国首例无先天性白内障的非典型Lowe综合征患者，并对OCRL基因的新变异进行了功能分析，从而扩大对Lowe综合征的临床表现和遗传多样性的认识。
方法：对来自中国南方三家医疗机构的8例Lowe综合征患者进行全外显子组测序。回顾性收集和分析临床和遗传数据，并对5个新的变异体进行了功能分析。
结果：在我们的队列中，八个Lowe综合征个体的临床症状各不相同。一名患者被诊断患有Lowe综合征，但未出现先天性白内障。所有患者的共同特征包括认知障碍，身材矮小,和低分子量蛋白尿。鉴定了OCRL基因的八个变异，包括三个以前报道的和五个新的变化。在小说中，三个无义突变被确定为致病性，两名具有不确定意义的新型错义变异的患者表现出严重的典型表型。此外，所有新变异均与蛋白表达水平改变相关,并影响初级纤毛形成.
结论：这项研究描述了中国首例无先天性白内障的非典型Lowe综合征患者，并对OCRL基因的新变异进行了功能分析，从而扩大对Lowe综合征的临床表现和遗传多样性的认识。
