A novel pathogenic frameshift variant unmasked by a large de novo deletion at 13q21.33-q31.1 in a Chinese patient with neuronal ceroid lipofuscinosis type 5

BMC Medical Genetics

Xin Fan¹  Tingting Jiang¹  Yiping Shen¹  Wei Li¹  Limei Huang¹  Jiasun Su¹  Shang Yi¹  Shujie Zhang¹  Jingrong Luo¹  Zailong Qin¹  Yue Zhang¹ 

[1] Genetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital, Children’s Hospital of Guangxi Zhuang Autonomous Region;

关键词: Neuronal ceroid lipofuscinoses;    CLN5;    CNV;    Exome sequencing;   

DOI  :  10.1186/s12881-020-01039-5

来源: DOAJ

【 摘 要 】

Abstract Background Neuronal ceroid lipofuscinosis type 5 (CLN5) is a rare form of neuronal ceroid lipofuscinoses (NCLs) which are a group of inherited neurodegenerative diseases characterized by progressive intellectual and motor deterioration, visual failure, seizures, behavioral changes and premature death. CLN5 was initially named Finnish variant late infantile NCL, it is now known to be present in other ethnic populations and with variable age of onset. Few CLN5 patients had been reported in Chinese population. Case presentation In this paper, we report the symptoms of a Chinese patient who suffer from developmental regression and grand mal epilepsy for several years. The DNA was extracted from peripheral blood of proband and both parents, and then whole exome sequencing was performed using genomic DNA. Both sequence variants and copy number variants (CNVs) were analyzed and classified according to guidelines. As the result, a novel frameshift mutation c.718_719delAT/p.Met240fs in CLN5 and a de novo large deletion at 13q21.33-q31.1 which unmasked the frameshift mutation were identified in the proband. Despite the large de novo deletion, which can be classified as a pathogenic copy number variant (CNV), the patient’s clinical presentation is mostly consistent with that of CLN5, except for early developmental delay which is believed due to the large deletion. Both variants were detected simultaneously by exome sequencing. Conclusions This is the first report of whole gene deletion in combination with a novel pathogenic sequence variant in a CLN5 patient. The two mutations detected with whole exome sequencing simultaneously proved the advantage of the sequencing technology for genetic diagnostics.

【 授权许可】

Unknown