Details of Disease

General Information of Disease (ID: DIS35YGW)

• Disease Name: Leber congenital amaurosis 9
• Synonyms: amaurosis congenita of Leber, type 9; Leber congenital amaurosis 9; NMNAT1 Leber congenital amaurosis; Leber congenital amaurosis caused by mutation in NMNAT1; Leber congenital amaurosis type 9; LCA9
• Definition: Any Leber congenital amaurosis in which the cause of the disease is a mutation in the NMNAT1 gene.
• Disease Hierarchy:
  DISA5PVY: NMNAT1-related retinopathy
  DISMGH8F: Leber congenital amaurosis
  DIS35YGW: Leber congenital amaurosis 9
• Disease Identifiers:
  MONDO ID: MONDO_0012056
  MESH ID: C536603
  UMLS CUI: C1837873
  OMIM ID: 608553
  MedGen ID: 325277

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 9 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
USP45	OT0KSON1	Strong	Autosomal recessive	[1]
CCT2	OTW1VV4E	Strong	Autosomal recessive	[7]
CLTA	OTLHOXMQ	Strong	Biomarker	[3]
CLUAP1	OTESP4WL	Strong	Autosomal recessive	[8]
LRAT	OTB7CJKY	Strong	Autosomal recessive	[9]
IQCB1	OTYQ28V9	Definitive	Autosomal recessive	[10]
NMNAT1	OTGJH9XH	Definitive	Autosomal recessive	[5]
PRPH2	OTNH2G5H	Definitive	Autosomal recessive	[11]
RPE65	OTHS41XM	Definitive	Autosomal recessive	[4]

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CNGA3	TTW0QOV	Limited	Autosomal recessive	[2]
GUCY2D	TTWNFC2	Strong	Biomarker	[3]
RPE65	TTBOH16	Strong	Biomarker	[4]
RPE65	TTBOH16	Definitive	Autosomal recessive	[4]

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
NMNAT1	DE4D159	Definitive	Autosomal recessive	[5]
NMNAT1	DE4D159	Definitive	Biomarker	[6]

References

• [1] Biallelic mutations in USP45, encoding a deubiquitinating enzyme, are associated with Leber congenital amaurosis. J Med Genet. 2019 May;56(5):325-331. doi: 10.1136/jmedgenet-2018-105709. Epub 2018 Dec 20.
• [2] Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in patients with Leber congenital amaurosis. Hum Mutat. 2011 Dec;32(12):1450-9. doi: 10.1002/humu.21587. Epub 2011 Sep 23.
• [3] Genome-wide linkage and sequence analysis challenge CCDC66 as a human retinal dystrophy candidate gene and support a distinct NMNAT1-related fundus phenotype. Clin Genet. 2018 Jan;93(1):149-154. doi: 10.1111/cge.13022. Epub 2017 May 9.
• [4] Mutations in RPE65 cause Leber's congenital amaurosis. Nat Genet. 1997 Oct;17(2):139-41. doi: 10.1038/ng1097-139.
• [5] Nonpenetrance of the most frequent autosomal recessive leber congenital amaurosis mutation in NMNAT1. JAMA Ophthalmol. 2014 Aug;132(8):1002-4. doi: 10.1001/jamaophthalmol.2014.983.
• [6] NMNAT1 E257K variant, associated with Leber Congenital Amaurosis (LCA9), causes a mild retinal degeneration phenotype.Exp Eye Res. 2018 Aug;173:32-43. doi: 10.1016/j.exer.2018.04.010. Epub 2018 Apr 17.
• [7] CCT2 Mutations Evoke Leber Congenital Amaurosis due to Chaperone Complex Instability. Sci Rep. 2016 Sep 20;6:33742. doi: 10.1038/srep33742.
• [8] Hypomorphic mutations identified in the candidate Leber congenital amaurosis gene CLUAP1. Genet Med. 2016 Oct;18(10):1044-51. doi: 10.1038/gim.2015.205. Epub 2016 Jan 28.
• [9] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [10] Comprehensive mutation analysis by whole-exome sequencing in 41 Chinese families with Leber congenital amaurosis. Invest Ophthalmol Vis Sci. 2013 Jun 26;54(6):4351-7. doi: 10.1167/iovs.13-11606.
• [11] Peripherin mutations cause a distinct form of recessive Leber congenital amaurosis and dominant phenotypes in asymptomatic parents heterozygous for the mutation. Br J Ophthalmol. 2016 Feb;100(2):209-15. doi: 10.1136/bjophthalmol-2015-306844. Epub 2015 Jun 10.