TY - JOUR
T1 - Identification of two novel null variants in CLN8 by targeted next-generation sequencing
T2 - First report of a Chinese patient with neuronal ceroid lipofuscinosis due to CLN8 variants
AU - Gao, Zhijie
AU - Xie, Hua
AU - Jiang, Qian
AU - Wu, Nan
AU - Chen, Xiaoli
AU - Chen, Qian
N1 - Funding Information:
We sincerely thank all the family members who contributed to the study. This work is supported by grants from the Beijing Municipal Science and Technology Commission (Z131107002213027 to Qian Chen), the Capital Health Research and Development of Special (2014-2-1131 to Xiaoli Chen), the Beijing Natural Science Foundation (7162029 to Xiaoli Chen), the Beijing Nova Program Interdisciplinary Collaborative Project (xxjc201717 to Xiaoli Chen), the Chinese National Nature Science Fund (31671310 to Xiaoli Chen, 81401207 to Hua Xie), and the advanced Personnel Training Program of Beijing Municipal Health Bureau to Xiaoli Chen
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/2/8
Y1 - 2018/2/8
N2 - Background: Neuronal ceroid lipofuscinoses (NCLs) are one of the most frequent childhood-onset neurodegenerative pathologies characterized by seizures, progressive cognitive decline, motor impairment and loss of vision. For the past two decades, more than 430 variants in 13 candidate genes have been identified in the affected patients. Most of the variants were almost exclusively reported in Western patients, and very little clinical and genetic information was available for Chinese patients. Case presentation: We report a Chinese boy whose clinical phenotypes were suspected to be NCL, including intractable epilepsy, cognitive and motor decline and progressive vision loss. Using targeted next-generation sequencing, two novel null variants in CLN8 (c.298C>T, p.Gln100Ter; c.551G>A, p.Trp184Ter) were detected in this patient in trans model. These two variants were interpreted as pathogenic according to the variant guidelines of the American College of Medical Genetics and Genomics. Conclusions: This is the first case report of NCL due to CLN8 variants in China. Our findings expand the variant diversity of CLN8 and demonstrate the tremendous diagnosis value of targeted next-generation sequencing for pediatric NCLs.
AB - Background: Neuronal ceroid lipofuscinoses (NCLs) are one of the most frequent childhood-onset neurodegenerative pathologies characterized by seizures, progressive cognitive decline, motor impairment and loss of vision. For the past two decades, more than 430 variants in 13 candidate genes have been identified in the affected patients. Most of the variants were almost exclusively reported in Western patients, and very little clinical and genetic information was available for Chinese patients. Case presentation: We report a Chinese boy whose clinical phenotypes were suspected to be NCL, including intractable epilepsy, cognitive and motor decline and progressive vision loss. Using targeted next-generation sequencing, two novel null variants in CLN8 (c.298C>T, p.Gln100Ter; c.551G>A, p.Trp184Ter) were detected in this patient in trans model. These two variants were interpreted as pathogenic according to the variant guidelines of the American College of Medical Genetics and Genomics. Conclusions: This is the first case report of NCL due to CLN8 variants in China. Our findings expand the variant diversity of CLN8 and demonstrate the tremendous diagnosis value of targeted next-generation sequencing for pediatric NCLs.
KW - CLN8
KW - Neuronal ceroid lipofuscinoses
KW - Novel null variant
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U2 - 10.1186/s12881-018-0535-7
DO - 10.1186/s12881-018-0535-7
M3 - Article
C2 - 29422019
AN - SCOPUS:85041855038
VL - 19
JO - BMC Medical Genetics
JF - BMC Medical Genetics
SN - 1471-2350
IS - 1
M1 - 21
ER -