Diagnostic journey and genetic analysis of a novel homozygous CYP2U1 mutation causing autosomal recessive spastic paraplegia type 56 (SPG56) in a consanguineous family

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...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Neurology
Subjects:
SPG56
CYP2U1
Hereditary spastic paraplegia
Consanguinity
Complex HSP
Ears of the Lynx
Online Access:https://doi.org/10.1186/s12883-025-04211-7
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1471-2377

Similar Items