Details of Disease

General Information of Disease (ID: DIS9KXQY)

• Disease Name: Complex hereditary spastic paraplegia
• Synonyms: syndromic hereditary spastic paraplegia; Complex HSP; complicated SPG; Complex SPG; complicated hereditary spastic paraplegia; Complex familial spastic paraplegia; syndrome associated with hereditary spastic paraplegia; complicated HSP; complicated familial spastic paraplegia
• Definition: A hereditary spastic paraplegia that is part of a larger syndrome.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISGZQV1: Hereditary spastic paraplegia
  DIS9KXQY: Complex hereditary spastic paraplegia
• Disease Identifiers:
  MONDO ID: MONDO_0015150
  UMLS CUI: C0393556
  MedGen ID: 581446
  Orphanet ID: 102013
  SNOMED CT ID: 230261006

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
ENTPD1	TTYM8DJ	Definitive	Autosomal recessive	[1]
MAG	TT9XFON	Definitive	Autosomal recessive	[1]

This Disease Is Related to 14 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GPT2	OTS5VF7N	Limited	Genetic Variation	[2]
ALS2	OT8BAM04	Disputed	Genetic Variation	[3]
EXOSC3	OTNCF906	Disputed	Genetic Variation	[4]
SERAC1	OTWH1ULQ	Disputed	Genetic Variation	[5]
DSTYK	OTUL75IR	Moderate	Autosomal recessive	[1]
ALDH18A1	OT6W40XU	Strong	Genetic Variation	[6]
ARL6IP1	OT536XAV	Strong	Genetic Variation	[7]
ATP13A2	OTKWBUGK	Strong	Biomarker	[8]
KIF1A	OT3JVEGV	Strong	Genetic Variation	[9]
SPG11	OTZ7LJX4	Strong	Genetic Variation	[10]
TFG	OT2KJENI	Strong	Genetic Variation	[11]
B4GALNT1	OTCY80HS	Definitive	Autosomal recessive	[1]
ENTPD1	OT6E2OW6	Definitive	Autosomal recessive	[1]
MAG	OTWVRR0K	Definitive	Autosomal recessive	[1]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] GPT2 mutations cause developmental encephalopathy with microcephaly and features of complicated hereditary spastic paraplegia.Clin Genet. 2018 Oct;94(3-4):356-361. doi: 10.1111/cge.13390. Epub 2018 Jul 10.
• [3] The first ALS2 missense mutation associated with JPLS reveals new aspects of alsin biological function.Brain. 2006 Jul;129(Pt 7):1710-9. doi: 10.1093/brain/awl104. Epub 2006 May 2.
• [4] Novel EXOSC3 mutation causes complicated hereditary spastic paraplegia.J Neurol. 2014 Nov;261(11):2165-9. doi: 10.1007/s00415-014-7457-x. Epub 2014 Aug 23.
• [5] SERAC1 deficiency causes complicated HSP: evidence from a novel splice mutation in a large family.J Med Genet. 2018 Jan;55(1):39-47. doi: 10.1136/jmedgenet-2017-104622. Epub 2017 Sep 15.
• [6] Novel mutations in the ALDH18A1 gene in complicated hereditary spastic paraplegia with cerebellar ataxia and cognitive impairment.J Hum Genet. 2018 Sep;63(9):1009-1013. doi: 10.1038/s10038-018-0477-0. Epub 2018 Jun 18.
• [7] Truncating ARL6IP1 variant as the genetic cause of fatal complicated hereditary spastic paraplegia.BMC Med Genet. 2019 Jul 4;20(1):119. doi: 10.1186/s12881-019-0851-6.
• [8] Loss-of-function mutations in the ATP13A2/PARK9 gene cause complicated hereditary spastic paraplegia (SPG78). Brain. 2017 Feb;140(2):287-305. doi: 10.1093/brain/aww307.
• [9] Autosomal dominant transmission of complicated hereditary spastic paraplegia due to a dominant negative mutation of KIF1A, SPG30 gene.Sci Rep. 2017 Oct 2;7(1):12527. doi: 10.1038/s41598-017-12999-9.
• [10] Monozygotic twins with a new compound heterozygous SPG11 mutation and different disease expression.J Neurol Sci. 2017 Oct 15;381:265-268. doi: 10.1016/j.jns.2017.09.005. Epub 2017 Sep 5.
• [11] A novel homozygous mutation of the TFG gene in a patient with early onset spastic paraplegia and later onset sensorimotor polyneuropathy.J Hum Genet. 2019 Feb;64(2):171-176. doi: 10.1038/s10038-018-0538-4. Epub 2018 Nov 22.