Expanding the clinical and molecular spectrum of TBC1D32-related ciliopathy: case reports and literature Review

IF 2.5 3区 生物学 Q2 GENETICS & HEREDITY
Wongsathorn Eiumtrakul, Thipwimol Tim-Aroon, Wadakarn Wuthisiri, Tharikarn Sujirakul, Thanissara Chansakul, Arthaporn Khongkraparn, Saisuda Noojarern, Duangrurdee Wattanasirichaigoon, Parith Wongkittichote
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引用次数: 0

Abstract

Genetic defects in primary cilia-related genes are associated with a heterogeneous group of disorders known as ciliopathies. TBC1D32-related ciliopathy presents with a broad phenotypic spectrum, ranging from isolated retinal diseases to severe multisystemic involvement, including fetal demise. We report two unrelated patients with retinal disease and hypopituitarism, with one also exhibiting facial dysmorphism, developmental delay, and unilateral oculomotor nerve palsy. Whole genome sequencing identified biallelic TBC1D32 variants in both patients, including two splice-site variants. RNA analysis revealed exon skipping, leading to frameshift and premature protein truncation. A review of previously reported cases highlighted facial dysmorphism, retinal disease, and hypopituitarism as major clinical features of TBC1D32-related ciliopathy. Additionally, we propose oculomotor nerve palsy as an extended clinical feature of this disorder. This study expands the clinical and molecular spectrum of TBC1D32-related ciliopathy.

Abstract Image

扩展tbc1d32相关纤毛病的临床和分子谱:病例报告和文献综述
原发性纤毛相关基因的遗传缺陷与称为纤毛病的异质组疾病有关。tbc1d32相关纤毛病表现出广泛的表型谱,从孤立的视网膜疾病到严重的多系统累及,包括胎儿死亡。我们报告了两例不相关的视网膜疾病和垂体功能低下患者,其中一人还表现出面部畸形、发育迟缓和单侧动眼神经麻痹。全基因组测序在两名患者中发现双等位基因TBC1D32变异,包括两个剪接位点变异。RNA分析显示外显子跳跃,导致移码和过早的蛋白质截断。对先前报道病例的回顾强调,面部畸形、视网膜疾病和垂体功能减退是tbc1d32相关纤毛病的主要临床特征。此外,我们提出动眼神经麻痹作为这种疾病的延伸临床特征。本研究扩大了tbc1d32相关纤毛病的临床和分子谱。
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来源期刊
Journal of Human Genetics
Journal of Human Genetics 生物-遗传学
CiteScore
7.20
自引率
0.00%
发文量
101
审稿时长
4-8 weeks
期刊介绍: The Journal of Human Genetics is an international journal publishing articles on human genetics, including medical genetics and human genome analysis. It covers all aspects of human genetics, including molecular genetics, clinical genetics, behavioral genetics, immunogenetics, pharmacogenomics, population genetics, functional genomics, epigenetics, genetic counseling and gene therapy. Articles on the following areas are especially welcome: genetic factors of monogenic and complex disorders, genome-wide association studies, genetic epidemiology, cancer genetics, personal genomics, genotype-phenotype relationships and genome diversity.
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