Novel likely disease-causing CLN5 variants identified in Pakistani patients with neuronal ceroid lipofuscinosis

JOURNAL OF THE NEUROLOGICAL SCIENCES

卷:414

Article

Azad, Beenish^1,2  Efthymiou, Stephanie²  Sultan, Tipu^3,4  Scala, Marcello^2,5,6  Alvi, Javeria Raza^3,4  Neuray, Caroline^2,7  Dominik, Natalia²  Gul, Asma¹  Houlden, Henry² 

[1] Int Islamic Univ Islamabad, Dept Biol Sci, H-10, Islamabad 44000, Pakistan

[2] UCL Inst Neurol, Dept Neuromuscular Disorders, Queen Sq, London WC1N 3BG, England

[3] Childrens Hosp, Dept Pediat Neurol, Lahore 54600, Pakistan

[4] Inst Child Hlth, Lahore 54600, Pakistan

[5] IRCCS Ist Giannina Gaslini, Pediat Neurol & Muscular Dis Unit, Genoa, Italy

[6] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy

[7] Paracelsus Med Univ, Dept Neurol, Christian Doppler Klin, Salzburg, Austria

关键词: CLN5;    Neuronal ceroid lipofuscinosis;    Exome sequencing;   

DOI  :  10.1016/j.jns.2020.116826

来源: Elsevier

【 摘 要 】

Background: Neuronal ceroid lipofuscinosis (NCL) is a hereditary lysosomal storage disease with progressive brain neurodegeneration. Mutations in ceroid lipofuscinosis neuronal protein 5 (CLN5) cause CLN5 disease, a severe condition characterized by seizures, visual failure, motor decline, and progressive cognitive deterioration. This study aimed to identify causative gene variants in Pakistani consanguineous families diagnosed with NCL. Methods: After a thorough clinical and neuroradiological characterization, whole exome sequencing (WES) was performed in 3 patients from 2 unrelated families. Segregation analysis was subsequently performed through Sanger sequencing Analysis: WES led to the identification of the 2 novel homozygous variants c.925_926del, (p.Leu309AlafsTer4) and c.477 T > C, (p.Cys159Arg). Conclusion: In this study, we report two novel CLN5 cases in the Punjab region of Pakistan. Our observations will help clinicians observe and compare common and unique clinical features of NCL patients, further improving our current understanding of NCL.

【 授权许可】

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