Details of Disease

General Information of Disease (ID: DIS1ODJO)

• Disease Name: Pelizeaus-Merzbacher spectrum disorder
• Synonyms: leukodystrophy, hypomyelinating, 1; Pelizaeus Merzbacher disease; leukodystrophy, sudanophilic; hypomyelinating leukodystrophy 1; HLD1; diffuse familial brain sclerosis; Pelizaeus-Merzbacher disease; sudanophilic leukodystrophy, Paelizeus-Merzbacher type; Sudanophilic leukodystrophy, Paelizeus-Merzbacher type; Pelizaeus Merzbacher brain sclerosis; PMD; Pelizaeus-Merzbacher disease, X-linked recessive; Pelizeaus-Merzbacher spectrum disorder; Pelizaeus-Merzbacher brain sclerosis
• Definition: An X-linked leukodystrophy characterized by developmental delay, nystagmus, hypotonia, spasticity, and variable intellectual deficit. It is classified into three sub-forms based on the age of onset and severity: connatal, transitional, and classic PMD.
• Disease Hierarchy:
  DISVY1TT: Leukodystrophy
  DIS1ODJO: Pelizeaus-Merzbacher spectrum disorder
• Disease Identifiers:
  MONDO ID: MONDO_0010714
  MESH ID: D020371
  UMLS CUI: C0205711
  OMIM ID: 312080
  MedGen ID: 61440
  HPO ID: HP:0003269
  Orphanet ID: 702
  SNOMED CT ID: 64855000

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
MBP	TT2RY5P	Limited	Genetic Variation	[1]
RNF6	TT4S09X	Limited	Biomarker	[2]
VEGFD	TTOM5H4	Limited	Biomarker	[3]
GJA3	TTFZRG0	Strong	Genetic Variation	[4]
GJC2	TTPOCAL	Strong	Genetic Variation	[5]

This Disease Is Related to 7 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CAPN3	OTCHG3YK	Strong	Altered Expression	[6]
CDT1	OTVY53VG	Strong	Genetic Variation	[7]
GPM6B	OT8Q1582	Strong	Genetic Variation	[8]
IFT122	OTSK3OAD	Strong	Biomarker	[9]
LMNB1	OT100T3P	Strong	Altered Expression	[10]
RARS1	OTHPZ6JN	Strong	Biomarker	[11]
PLP1	OT8CM9CX	Definitive	X-linked	[12]

References

• [1] Connatal Pelizaeus-Merzbacher disease associated with the jimpy(msd) mice mutation.Pediatr Neurol. 1999 Apr;20(4):309-11. doi: 10.1016/s0887-8994(98)00160-x.
• [2] Unusual clinical and magnetic resonance imaging findings in a family with proteolipid protein gene mutation.Arch Neurol. 2003 Feb;60(2):268-72. doi: 10.1001/archneur.60.2.268.
• [3] Placental mesenchymal dysplasia with a good outcome: A case report.J Obstet Gynaecol Res. 2019 Nov;45(11):2284-2288. doi: 10.1111/jog.14095. Epub 2019 Aug 26.
• [4] [Pelizaeus-Merzbacher-caused diseases in Connexin 46 mutation: a rare form of leukodystrophy].Rofo. 2007 Jun;179(6):637-8. doi: 10.1055/s-2007-963009. Epub 2007 May 9.
• [5] Neurogenetics of Pelizaeus-Merzbacher disease.Handb Clin Neurol. 2018;148:701-722. doi: 10.1016/B978-0-444-64076-5.00045-4.
• [6] Expression of three calpain isoform genes in human skeletal muscles.J Neurol Sci. 1998 Mar 5;155(2):163-9. doi: 10.1016/s0022-510x(97)00309-2.
• [7] Complex genomic rearrangements at the PLP1 locus include triplication and quadruplication.PLoS Genet. 2015 Mar 6;11(3):e1005050. doi: 10.1371/journal.pgen.1005050. eCollection 2015 Mar.
• [8] PLP1 and GPM6B intragenic copy number analysis by MAPH in 262 patients with hypomyelinating leukodystrophies: Identification of one partial triplication and two partial deletions of PLP1.Neurogenetics. 2006 Mar;7(1):31-7. doi: 10.1007/s10048-005-0021-1. Epub 2006 Jan 17.
• [9] Genotype-phenotype correlation in inherited brain myelination defects due to proteolipid protein gene mutations. Clinical European Network on Brain Dysmyelinating Disease.Eur J Hum Genet. 2000 Nov;8(11):837-45. doi: 10.1038/sj.ejhg.5200537.
• [10] Lamin B1 mediates cell-autonomous neuropathology in a leukodystrophy mouse model.J Clin Invest. 2013 Jun;123(6):2719-29. doi: 10.1172/JCI66737. Epub 2013 May 15.
• [11] Mutations in RARS cause a hypomyelination disorder akin to Pelizaeus-Merzbacher disease.Eur J Hum Genet. 2017 Oct;25(10):1134-1141. doi: 10.1038/ejhg.2017.119. Epub 2017 Jul 26.
• [12] 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.