Details of Disease

General Information of Disease (ID: DISYFO3L)

• Disease Name: Hereditary spastic paraplegia 10
• Synonyms: spastic paraplegia 10, autosomal dominant; spastic paraplegia 10; spastic paraplegia 10 with or without peripheral neuropathy; autosomal dominant spastic paraplegia; autosomal dominant spastic paraplegia type 10; SPG10; autosomal dominant spastic paraplegia 10; hereditary spastic paraplegia caused by mutation in KIF5A; KIF5A hereditary spastic paraplegia; hereditary spastic paraplegia type 10
• Definition: Autosomal dominant spastic paraplegia type 10 (SPG10) is a rare type of hereditary spastic paraplegia that can present as either a pure form of spastic paraplegia with lower limb spasticity, hyperreflexia and extensor plantar responses, presenting in childhood or adolescence, or as a complex phenotype associated with additional manifestations including peripheral neuropathy with upper limb amyotrophy, moderate intellectual disability and parkinsonism. Deafness and retinitis pigmentosa were reported in one case.
• Disease Hierarchy:
  DISGZQV1: Hereditary spastic paraplegia
  DISYFO3L: Hereditary spastic paraplegia 10
• Disease Identifiers:
  MONDO ID: MONDO_0011408
  MESH ID: C537482
  UMLS CUI: C1858712
  OMIM ID: 604187
  MedGen ID: 349003
  Orphanet ID: 100991
  SNOMED CT ID: 732948003

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
KIF5A	TTCJPAH	Strong	Autosomal dominant	[1]
KIF5A	TTCJPAH	Strong	Biomarker	[2]

This Disease Is Related to 10 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
KIF1B	OTI1XQTO	Limited	Biomarker	[2]
MAD2L1BP	OT2O2IUJ	Limited	Biomarker	[2]
CPT1C	OT8F1MBF	Strong	Genetic Variation	[3]
KIF5A	OT3ETTI6	Strong	Autosomal dominant	[1]
KIF5B	OTT34MT8	Strong	Genetic Variation	[4]
KIF5C	OT35570Y	Strong	Genetic Variation	[4]
REEP1	OTEMVFX7	Strong	Biomarker	[5]
SNTB1	OTSRBECI	Strong	Biomarker	[6]
SPAST	OTIF3AJI	Strong	Biomarker	[7]
KIF1A	OT3JVEGV	Definitive	Genetic Variation	[8]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] Genome-wide Analyses Identify KIF5A as a Novel ALS Gene.Neuron. 2018 Mar 21;97(6):1267-1288. doi: 10.1016/j.neuron.2018.02.027.
• [3] Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia. JAMA Neurol. 2015 May;72(5):561-70. doi: 10.1001/jamaneurol.2014.4769.
• [4] A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10).Am J Hum Genet. 2002 Nov;71(5):1189-94. doi: 10.1086/344210. Epub 2002 Sep 24.
• [5] De novo REEP2 missense mutation in pure hereditary spastic paraplegia.Ann Clin Transl Neurol. 2017 Apr 11;4(5):347-350. doi: 10.1002/acn3.404. eCollection 2017 May.
• [6] Brazilian family with pure autosomal dominant spastic paraplegia maps to 8q: analysis of muscle beta 1 syntrophin.Am J Med Genet. 2000 May 15;92(2):122-7. doi: 10.1002/(sici)1096-8628(20000515)92:2<122::aid-ajmg8>3.0.co;2-b.
• [7] Spastin mutations are frequent in sporadic spastic paraparesis and their spectrum is different from that observed in familial cases.J Med Genet. 2006 Mar;43(3):259-65. doi: 10.1136/jmg.2005.035311. Epub 2005 Jul 31.
• [8] KIF1A variants are a frequent cause of autosomal dominant hereditary spastic paraplegia.Eur J Hum Genet. 2020 Jan;28(1):40-49. doi: 10.1038/s41431-019-0497-z. Epub 2019 Sep 5.