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 10 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
USP45	OT0KSON1	Strong	Autosomal recessive	[1]
CNGA3	OTYQ7TYM	Limited	Autosomal recessive	[2]
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.