European journal of medical genetics · 2025
Persistent lymphopenia in a Japanese boy with neuronal ceroid lipofuscinosis type 3.
Клинический случайСтатьяНазвание и аннотация: Перевод в очереди
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Kajiwara Kenta, Liang Qiaowei, Uchiyama Yuri, Chong Pin Fee, Ichimiya Yuko, Monji Norihisa, Shimokawa Sakurako, Sonoda Motoshi, Watanabe Eriko, Sakata Ayumi, Sonoda Yuri, Akamine Satoshi, Ishimura Masataka, Murakami Yusuke, Kunisaki Yuya, Sonoda Koh-Hei, Matsumoto Naomichi, Sakai Yasunari, Ohga Shouichi
Аннотация
BACKGROUND: Neuronal ceroid lipofuscinosis (NCL) is a heterogeneous group of lysosomal disorders characterized by progressive psychomotor regression, visual impairment, and intractable seizures. Genetically, NCL type 3 (CLN3) is associated with variants in the gene encoding a lysosomal transmembrane protein. To date, few Japanese patients with CLN3 have been reported. Thus, their neurodevelopmental and clinical features remain unclear. Here, we report the clinical course of a genetically confirmed Japanese patient with CLN3.
CLINICAL REPORT: A 17-year-old Japanese boy was diagnosed with retinitis pigmentosa at age 7. Visual impairment progressed over a 10-year follow-up period. Generalized tonic-clonic seizures also began at age 7. Developmental regression was recognized at age 13, with an accelerated decline in motor and communication skills following a COVID-19 infection at age 17. Tube feeding and gastrostomy were initiated for dysphagia and recurrent respiratory infections. Serial MRI revealed progressive cerebral and cerebellar atrophy. Lymphopenia (351-1467/μL) was present from age 9; peripheral blood smear revealed vacuolated lymphocytes.
RESULTS: Exome sequencing identified a heterozygous CLN3 variant, NM_001042432.2:c.295-2A > C. SpliceAI suggested exon 6 skipping and/or an 80-bp deletion, leading to nonsense-mediated mRNA decay. Manual inspection using Integrated Genomic Viewer revealed a second variant (c.178_180delinsACATCCTTAGCCACAAGAG) missed initially. Trio Sanger sequencing confirmed compound heterozygosity: NM_001042432.2:c.[295-2A > C]; [178_180delinsACATCCTTAGCCACAAGAG] p.[?]; [His60Thrfs∗10]. A review of 430 genetically confirmed CLN3 patients (1989-2025) identified no hematologic abnormalities.
CONCLUSION: This Japanese CLN3 patient developed visual impairment 7-8 years before systemic deterioration. Retinal degeneration, together with vacuolated peripheral lymphocytes, may provide early diagnostic clues for CLN3 in Japanese patients.
CLINICAL REPORT: A 17-year-old Japanese boy was diagnosed with retinitis pigmentosa at age 7. Visual impairment progressed over a 10-year follow-up period. Generalized tonic-clonic seizures also began at age 7. Developmental regression was recognized at age 13, with an accelerated decline in motor and communication skills following a COVID-19 infection at age 17. Tube feeding and gastrostomy were initiated for dysphagia and recurrent respiratory infections. Serial MRI revealed progressive cerebral and cerebellar atrophy. Lymphopenia (351-1467/μL) was present from age 9; peripheral blood smear revealed vacuolated lymphocytes.
RESULTS: Exome sequencing identified a heterozygous CLN3 variant, NM_001042432.2:c.295-2A > C. SpliceAI suggested exon 6 skipping and/or an 80-bp deletion, leading to nonsense-mediated mRNA decay. Manual inspection using Integrated Genomic Viewer revealed a second variant (c.178_180delinsACATCCTTAGCCACAAGAG) missed initially. Trio Sanger sequencing confirmed compound heterozygosity: NM_001042432.2:c.[295-2A > C]; [178_180delinsACATCCTTAGCCACAAGAG] p.[?]; [His60Thrfs∗10]. A review of 430 genetically confirmed CLN3 patients (1989-2025) identified no hematologic abnormalities.
CONCLUSION: This Japanese CLN3 patient developed visual impairment 7-8 years before systemic deterioration. Retinal degeneration, together with vacuolated peripheral lymphocytes, may provide early diagnostic clues for CLN3 in Japanese patients.