The proband was a 5-year-old Chinese boy admitted to the hospital with a chief complaint of language articulation disorders for 1.5 years, uncoordinated movements for half a year, and repeated episodes of seizures for one week. A stutter was noted without obvious causes one and a half years before, and he had gradually developed unclear enunciation, clumsy speech, and slow response. Within the previous 6 months, he began to have uncoordinated movements, such as ataxia and instable gait. Three episodes of generalized tonic–clonic seizures had occurred in the week just preceding the clinic visit; every episode lasted for about 1 min and occurred about once every 2 days. He achieved appropriate developmental milestones before age 3.5 years and was born at full-term by vaginal delivery without any complications. There was no exposure to alcohol or medications during the pregnancy, and Apgar scores were 10 and 10 at 1 and 5 min, respectively. His parents had no known consanguinity, and both they and an older sister were healthy. On physical examination, length, weight, and head circumference were normal for age, and he was conscious and showed normal muscle strength and muscle tone. Patellar reflex and Achilles tendon reflex were normal, and Babinski signs were negative. He was inarticulate and responded to questions slowly. He could not complete the hand-alternating movement test, heel–knee–tibia test, or finger–nose test because of poor cooperation with the instructions. The intelligence quotient value, measured by combined Raven’s test, was 80 (a medium level). The tests for blood lactic acid, homocysteine, ammonia, ceruloplasmin, and liver and kidney function were normal. Tests for antibodies for autoimmune encephalitis in cerebrospinal fluid and blood were negative. The screening for genetic metabolic diseases in blood and urine showed no obvious abnormalities. An electroencephalogram (EEG) showed multiple spikes and slow-wave discharges bilaterally. A brain MRI scan showed high hyperintensities adjacent to the bilateral posterior horns of the lateral ventricles on T2-weighted images and broadened cerebellar fissures. Leukoencephalopathy was considered, and genetic analysis for hereditary leukoencephalopathies was recommended. With written consent from his parents, peripheral blood samples were collected from the proband and his parents. DNA was extracted using the Puregene Extraction Kit (Qiagen, USA). The NextSeq500 sequencer (Illumina Inc., USA) was used to screen the exons in the genes related to hereditary leukoencephalopathies. The genes in the panel are listed in Additional file. The data obtained were analyzed using accompanying software, and the variants were called according to the protocol. The variants were interpreted according to the guidelines from the American College of Medical Genetics and Genomics and patient phenotype []. Direct sequencing validated the detected missense mutations. Direct sequencing was performed on DNA from the proband and his parents using the ABI3500sequencer (Life Technology, USA), and the samples were subjected to sequence analysis using Sequence Scanner v1.0 (Applied Biosystems, USA). The matched Chinese controls were obtained from the Shenyang Kingmed for Clinical Laboratory (Shenyang, China). The sequencing procedure and mutation validation were performed by Shenyang Kingmed for Clinical Laboratory (Shenyang, China), which provides third party inspection services. The possible effects of the mutations on protein function were analyzed using the Polymorphism Phenotyping v2 (PolyPhen-2) prediction tool (), SIFT (), and MutationTaster (). The genetic analysis showed that the proband had a homozygous missense point mutation c.892G > A(p.Glu298Lys) (reference sequence: NM_017882.2) in exon 7 in CLN6 and that both his parents were heterozygous for the mutation. The mutation was not detected in 259 control subjects. LINCL was diagnosed, and a visual test was performed and showed no obvious abnormalities. PolyPhen-2, SIFT, and MutationTaster analysis suggested that the mutation would negatively affect protein function. The mutation in the patient is the first reported, and we can define it as recessive. Because of the history of seizures and the EEG results, the patient was diagnosed with epilepsy, and oral sodium valproate (VPA) was ordered. VPA administration was initiated at 15 mg/kg per day, administered in two doses, increasing to about 25 mg/kg per day in 2 weeks. The blood concentration range was 56–78 μg/ml over 6 months. At the 6-month follow-up, the episodes were decreased to about once a month, articulation disorders and uncoordinated movements persisted, and visual loss was not detected. At the locus of CLN6, 31 missense mutations including the reported ones and ours were analyzed; 22.6% (7/31) were located in the cytoplasmic domains, 32.2% (10/31) in the TM domains, and 45.2% (14/31) in the luminal domains of the protein. Regarding each domain of the protein, the mutations were mostly located in the TM3-TM4 loop (6/31), TM1-TM2 loop (4/31), and C-terminus (4/31), and no mutations were reported in the TM4-TM5 loop, TM5-TM6 loop, and TM7 domain.