Diagnostic journey and genetic analysis of a novel homozygous CYP2U1 mutation causing autosomal recessive spastic paraplegia type 56 (SPG56) in a consanguineous family
Abstract Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder, with spastic paraplegia type 56 (SPG56) being an exceptionally rare, autosomal recessive subtype caused by mutations in the CYP2U1 gene. This study reports a complex case of an adult female from a consanguineous family who...
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2025-05-01
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| Online Access: | https://doi.org/10.1186/s12883-025-04211-7 |
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| author | Hong-ping Yu Jing Zou Xiang Chen Ying Chen Dan-dan Ruan Qian Chen Jian-hui Zhang Qiong Cheng Xing-lin Ruan Wei Wen Li Chen Jie-wei Luo Yun-fei Li Xiao-lin Jiang |
| author_facet | Hong-ping Yu Jing Zou Xiang Chen Ying Chen Dan-dan Ruan Qian Chen Jian-hui Zhang Qiong Cheng Xing-lin Ruan Wei Wen Li Chen Jie-wei Luo Yun-fei Li Xiao-lin Jiang |
| author_sort | Hong-ping Yu |
| collection | DOAJ |
| description | Abstract Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder, with spastic paraplegia type 56 (SPG56) being an exceptionally rare, autosomal recessive subtype caused by mutations in the CYP2U1 gene. This study reports a complex case of an adult female from a consanguineous family who presented with cognitive developmental delays, short stature, and progressive neurological symptoms. At age 39, she developed unilateral tremors, which progressed to generalized tremors and leg weakness with a tiptoe gait. The clinical findings included hypertonia in the upper limbs, exaggerated reflexes in the lower limbs, vague speech, and emotional disturbances. Brain MRI revealed corpus callosum thinning, “ears of the Lynx” sign, bilateral globus pallidus calcifications, and mild brain atrophy. Comprehensive genomic analysis, including whole exome sequencing (WES), copy number variation (CNV) assessment, mitochondrial DNA sequencing, variant filtering, and Sanger sequencing, identified a homozygous c.913 C > T (p.His305Tyr) mutation in CYP2U1 (NM_183075). The heterozygous carriers presented no symptoms. This case contributes to the phenotypic spectrum of SPG56, offering new insights into its diagnosis and genetic underpinnings. |
| format | Article |
| id | doaj-art-da8a0b963ba94f73aa2df06bc1b6486e |
| institution | DOAJ |
| issn | 1471-2377 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neurology |
| spelling | doaj-art-da8a0b963ba94f73aa2df06bc1b6486e2025-08-20T03:07:56ZengBMCBMC Neurology1471-23772025-05-012511710.1186/s12883-025-04211-7Diagnostic journey and genetic analysis of a novel homozygous CYP2U1 mutation causing autosomal recessive spastic paraplegia type 56 (SPG56) in a consanguineous familyHong-ping Yu0Jing Zou1Xiang Chen2Ying Chen3Dan-dan Ruan4Qian Chen5Jian-hui Zhang6Qiong Cheng7Xing-lin Ruan8Wei Wen9Li Chen10Jie-wei Luo11Yun-fei Li12Xiao-lin Jiang13Department of Traditional Chinese Medicine and Neurology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalDepartment of Traditional Chinese Medicine and Neurology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalThe First Clinical Medical College, Nanchang UniversityDepartment of Traditional Chinese Medicine and Neurology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalDepartment of Traditional Chinese Medicine and Neurology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalDepartment of Traditional Chinese Medicine and Neurology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalDepartment of Traditional Chinese Medicine and Neurology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalDepartment of Traditional Chinese Medicine and Neurology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalDepartment of Neurology, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalDepartment of Rehabilitation Medicine, Ganzhou Municipal HospitalDepartment of Traditional Chinese Medicine and Neurology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalDepartment of Traditional Chinese Medicine and Neurology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalDepartment of Traditional Chinese Medicine and Neurology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalDepartment of Traditional Chinese Medicine and Neurology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalAbstract Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder, with spastic paraplegia type 56 (SPG56) being an exceptionally rare, autosomal recessive subtype caused by mutations in the CYP2U1 gene. This study reports a complex case of an adult female from a consanguineous family who presented with cognitive developmental delays, short stature, and progressive neurological symptoms. At age 39, she developed unilateral tremors, which progressed to generalized tremors and leg weakness with a tiptoe gait. The clinical findings included hypertonia in the upper limbs, exaggerated reflexes in the lower limbs, vague speech, and emotional disturbances. Brain MRI revealed corpus callosum thinning, “ears of the Lynx” sign, bilateral globus pallidus calcifications, and mild brain atrophy. Comprehensive genomic analysis, including whole exome sequencing (WES), copy number variation (CNV) assessment, mitochondrial DNA sequencing, variant filtering, and Sanger sequencing, identified a homozygous c.913 C > T (p.His305Tyr) mutation in CYP2U1 (NM_183075). The heterozygous carriers presented no symptoms. This case contributes to the phenotypic spectrum of SPG56, offering new insights into its diagnosis and genetic underpinnings.https://doi.org/10.1186/s12883-025-04211-7SPG56CYP2U1Hereditary spastic paraplegiaConsanguinityComplex HSPEars of the Lynx |
| spellingShingle | Hong-ping Yu Jing Zou Xiang Chen Ying Chen Dan-dan Ruan Qian Chen Jian-hui Zhang Qiong Cheng Xing-lin Ruan Wei Wen Li Chen Jie-wei Luo Yun-fei Li Xiao-lin Jiang Diagnostic journey and genetic analysis of a novel homozygous CYP2U1 mutation causing autosomal recessive spastic paraplegia type 56 (SPG56) in a consanguineous family BMC Neurology SPG56 CYP2U1 Hereditary spastic paraplegia Consanguinity Complex HSP Ears of the Lynx |
| title | Diagnostic journey and genetic analysis of a novel homozygous CYP2U1 mutation causing autosomal recessive spastic paraplegia type 56 (SPG56) in a consanguineous family |
| title_full | Diagnostic journey and genetic analysis of a novel homozygous CYP2U1 mutation causing autosomal recessive spastic paraplegia type 56 (SPG56) in a consanguineous family |
| title_fullStr | Diagnostic journey and genetic analysis of a novel homozygous CYP2U1 mutation causing autosomal recessive spastic paraplegia type 56 (SPG56) in a consanguineous family |
| title_full_unstemmed | Diagnostic journey and genetic analysis of a novel homozygous CYP2U1 mutation causing autosomal recessive spastic paraplegia type 56 (SPG56) in a consanguineous family |
| title_short | Diagnostic journey and genetic analysis of a novel homozygous CYP2U1 mutation causing autosomal recessive spastic paraplegia type 56 (SPG56) in a consanguineous family |
| title_sort | diagnostic journey and genetic analysis of a novel homozygous cyp2u1 mutation causing autosomal recessive spastic paraplegia type 56 spg56 in a consanguineous family |
| topic | SPG56 CYP2U1 Hereditary spastic paraplegia Consanguinity Complex HSP Ears of the Lynx |
| url | https://doi.org/10.1186/s12883-025-04211-7 |
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