Details of Disease

Disease Name

Amelogenesis imperfecta

Definition

Amelogenesis imperfecta (AI) represents a group of developmental conditions affecting the structure and clinical appearance of the enamel of all or nearly all the teeth in a more or less equal manner, and which may be associated with morphologic or biochemical changes elsewhere in the body.

Disease Hierarchy

DISYKSRF: Genetic disease

DISN6ZMR: Dental enamel hypoplasia

DISGYR9E: Amelogenesis imperfecta

Disease Identifiers

MONDO ID

MONDO_0019507

MESH ID

D000567

UMLS CUI

C0002452

MedGen ID

240

HPO ID

HP:0000705

Orphanet ID

88661

SNOMED CT ID

78494001

General Information of Disease (ID: DISGYR9E)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 29 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
WDR72	OTLMZGTC	Definitive	Autosomal recessive	[1]
AMELY	OTVG0EXE	Limited	Biomarker	[15]
FAM20A	OT5Z5IW8	Limited	Genetic Variation	[16]
MMP20	OT16S5S3	Limited	Genetic Variation	[17]
AMTN	OTXAMT4V	moderate	Genetic Variation	[18]
DLX3	OTARP5SQ	moderate	Genetic Variation	[19]
ENAM	OTK8PU0T	moderate	Genetic Variation	[14]
PEX26	OT5AM0BM	moderate	Biomarker	[20]
ROGDI	OTZ7LSKJ	moderate	Biomarker	[4]
AMBN	OTWASIMQ	Strong	Genetic Variation	[21]
AMELX	OTIN26MM	Strong	Genetic Variation	[9]
ARHGAP6	OTNVXXFX	Strong	Genetic Variation	[22]
CLDN16	OTTHAIKR	Strong	Genetic Variation	[23]
CLDN19	OTVD6IBL	Strong	Altered Expression	[24]
CNNM4	OTUXJRM1	Strong	Genetic Variation	[25]
COL17A1	OTID5AH2	Strong	Genetic Variation	[26]
CRX	OTH435SV	Strong	Genetic Variation	[10]
FAM20C	OTW5YZ7X	Strong	Genetic Variation	[27]
FAM83H	OTN0SF11	Strong	Altered Expression	[28]
GPR68	OT1NXSMN	Strong	Genetic Variation	[29]
HPX	OT14T7Q1	Strong	Genetic Variation	[30]
HTN1	OTH3W1RR	Strong	Genetic Variation	[6]
LTBP3	OTME98V7	Strong	Genetic Variation	[31]
MMP25	OT3BG37V	Strong	Genetic Variation	[32]
PEX1	OTQJF0V7	Strong	Biomarker	[33]
RELT	OT419II2	Strong	Genetic Variation	[34]
ODAPH	OTOALKQN	Definitive	Genetic Variation	[35]
STIM1	OT8CLQ1W	Definitive	Genetic Variation	[11]
TMEM165	OTMVJ0GA	Definitive	Biomarker	[36]
------------------------------------------------------------------------------------


⏷ Show the Full List of 29 DOT(s)

This Disease Is Related to 12 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
KLK4	TT4319X	Limited	CausalMutation	[2]
LAMC2	TTNS7H3	moderate	Biomarker	[3]
SLC13A5	TTFIMH7	moderate	Biomarker	[4]
CSNK1D	TTH30UI	Strong	Biomarker	[5]
CSNK1G2	TT0UZJ9	Strong	Biomarker	[5]
CSNK1G3	TT34L5N	Strong	Biomarker	[5]
HEXIM1	TTFOKAH	Strong	Genetic Variation	[6]
ITGB6	TTKQSXZ	Strong	Genetic Variation	[7]
KCNJ1	TTJ13ST	Strong	Biomarker	[8]
LAMB3	TT2WOUQ	Strong	Genetic Variation	[9]
RPGR	TTHBDA9	Strong	Genetic Variation	[10]
ORAI1	TTE76YK	Definitive	Genetic Variation	[11]
------------------------------------------------------------------------------------


⏷ Show the Full List of 12 DTT(s)

This Disease Is Related to 3 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC10A7	DTG1RJO	Strong	Genetic Variation	[12]
SLC24A3	DTO18LP	Strong	Biomarker	[13]
SLC24A4	DTQWF14	Definitive	Genetic Variation	[14]
------------------------------------------------------------------------------------

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ACP4	DE3OZT4	Strong	Genetic Variation	[14]
------------------------------------------------------------------------------------

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	A Fourth KLK4 Mutation Is Associated with Enamel Hypomineralisation and Structural Abnormalities.Front Physiol. 2017 May 29;8:333. doi: 10.3389/fphys.2017.00333. eCollection 2017.
3	Laminin 2 knockout mice rescued with the human protein exhibit enamel maturation defects.Matrix Biol. 2016 May-Jul;52-54:207-218. doi: 10.1016/j.matbio.2016.03.002. Epub 2016 Mar 5.
4	SLC13A5 is the second gene associated with Kohlschtter-T?nz syndrome. J Med Genet. 2017 Jan;54(1):54-62. doi: 10.1136/jmedgenet-2016-103988. Epub 2016 Sep 6.
5	FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes.Sci Rep. 2016 May 25;6:26557. doi: 10.1038/srep26557.
6	Enamelin maps to human chromosome 4q21 within the autosomal dominant amelogenesis imperfecta locus.Eur J Oral Sci. 2000 Oct;108(5):353-8. doi: 10.1034/j.1600-0722.2000.108005353.x.
7	Expansion of the spectrum of ITGB6-related disorders to adolescent alopecia, dentogingival abnormalities and intellectual disability.Eur J Hum Genet. 2016 Aug;24(8):1223-7. doi: 10.1038/ejhg.2015.260. Epub 2015 Dec 23.
8	Typical Features of Amelogenesis Imperfecta in Two Patients with Bartter's Syndrome.Nephron Extra. 2012 Jan;2(1):319-25. doi: 10.1159/000345801. Epub 2012 Dec 18.
9	Protocol GenoDENT: Implementation of a New NGS Panel for Molecular Diagnosis of Genetic Disorders with Orodental Involvement.Methods Mol Biol. 2019;1922:407-452. doi: 10.1007/978-1-4939-9012-2_36.
10	Identification of a locus on chromosome 2q11 at which recessive amelogenesis imperfecta and cone-rod dystrophy cosegregate.Eur J Hum Genet. 2002 Dec;10(12):865-9. doi: 10.1038/sj.ejhg.5200884.
11	CRAC channels in dental enamel cells.Cell Calcium. 2018 Nov;75:14-20. doi: 10.1016/j.ceca.2018.07.012. Epub 2018 Aug 9.
12	SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects.Nat Commun. 2018 Aug 6;9(1):3087. doi: 10.1038/s41467-018-05191-8.
13	Identification of mutations in SLC24A4, encoding a potassium-dependent sodium/calcium exchanger, as a cause of amelogenesis imperfecta. Am J Hum Genet. 2013 Feb 7;92(2):307-12. doi: 10.1016/j.ajhg.2013.01.003. Epub 2013 Jan 31.
14	Canine models of human amelogenesis imperfecta: identification of novel recessive ENAM and ACP4 variants.Hum Genet. 2019 May;138(5):525-533. doi: 10.1007/s00439-019-01997-8. Epub 2019 Mar 15.
15	A mutation in the mouse Amelx tri-tyrosyl domain results in impaired secretion of amelogenin and phenocopies human X-linked amelogenesis imperfecta.Hum Mol Genet. 2010 Apr 1;19(7):1230-47. doi: 10.1093/hmg/ddq001. Epub 2010 Jan 12.
16	FAM20A is essential for amelogenesis, but is dispensable for dentinogenesis.J Mol Histol. 2019 Dec;50(6):581-591. doi: 10.1007/s10735-019-09851-x. Epub 2019 Oct 30.
17	Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta.Front Physiol. 2017 Jun 14;8:398. doi: 10.3389/fphys.2017.00398. eCollection 2017.
18	Examination of rare genetic variants in dental enamel genes: The potential role of next-generation sequencing in primary dental care.Orthod Craniofac Res. 2019 May;22 Suppl 1:49-55. doi: 10.1111/ocr.12266.
19	Novel DLX3 variants in amelogenesis imperfecta with attenuated tricho-dento-osseous syndrome.Oral Dis. 2019 Jan;25(1):182-191. doi: 10.1111/odi.12955. Epub 2018 Sep 9.
20	Next-generation sequencing reveals the mutational landscape of clinically diagnosed Usher syndrome: copy number variations, phenocopies, a predominant target for translational read-through, and PEX26 mutated in Heimler syndrome.Mol Genet Genomic Med. 2017 Jul 6;5(5):531-552. doi: 10.1002/mgg3.312. eCollection 2017 Sep.
21	AMBN mutations causing hypoplastic amelogenesis imperfecta and Ambn knockout-NLS-lacZ knockin mice exhibiting failed amelogenesis and Ambn tissue-specificity.Mol Genet Genomic Med. 2019 Sep;7(9):e929. doi: 10.1002/mgg3.929. Epub 2019 Aug 11.
22	Amelogenesis imperfecta in two families with defined AMELX deletions in ARHGAP6. PLoS One. 2012;7(12):e52052. doi: 10.1371/journal.pone.0052052. Epub 2012 Dec 14.
23	Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation.J Bone Miner Res. 2016 Mar;31(3):498-513. doi: 10.1002/jbmr.2726. Epub 2015 Oct 20.
24	Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused by CLDN19 gene mutations.J Med Genet. 2017 Jan;54(1):26-37. doi: 10.1136/jmedgenet-2016-103956. Epub 2016 Aug 16.
25	Jalili Syndrome: Cross-sectional and Longitudinal Features of Seven Patients With Cone-Rod Dystrophy and Amelogenesis Imperfecta.Am J Ophthalmol. 2018 Apr;188:123-130. doi: 10.1016/j.ajo.2018.01.029. Epub 2018 Feb 5.
26	A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.J Med Genet. 2016 Feb;53(2):98-110. doi: 10.1136/jmedgenet-2015-103302. Epub 2015 Oct 26.
27	Periodontal disease and FAM20A mutations.J Hum Genet. 2017 Jul;62(7):679-686. doi: 10.1038/jhg.2017.26. Epub 2017 Mar 16.
28	Immunohistochemical Localization of Fam83h During Fluorosis-induced Mouse Molar Development.J Histochem Cytochem. 2018 Sep;66(9):663-671. doi: 10.1369/0022155418772289. Epub 2018 Apr 20.
29	Mutations in the pH-Sensing G-protein-Coupled Receptor GPR68 Cause Amelogenesis Imperfecta. Am J Hum Genet. 2016 Oct 6;99(4):984-990. doi: 10.1016/j.ajhg.2016.08.020. Epub 2016 Sep 29.
30	MMP20 hemopexin domain mutation in amelogenesis imperfecta.J Dent Res. 2010 Jan;89(1):46-50. doi: 10.1177/0022034509352844.
31	Enamel and dental anomalies in latent-transforming growth factor beta-binding protein 3 mutant mice.Eur J Oral Sci. 2017 Feb;125(1):8-17. doi: 10.1111/eos.12328.
32	Homozygous and compound heterozygous MMP20 mutations in amelogenesis imperfecta.J Dent Res. 2013 Jul;92(7):598-603. doi: 10.1177/0022034513488393. Epub 2013 Apr 26.
33	Severe early onset retinitis pigmentosa in a Moroccan patient with Heimler syndrome due to novel homozygous mutation of PEX1 gene.Eur J Med Genet. 2016 Oct;59(10):507-11. doi: 10.1016/j.ejmg.2016.09.004. Epub 2016 Sep 12.
34	Mutations in RELT cause autosomal recessive amelogenesis imperfecta. Clin Genet. 2019 Mar;95(3):375-383. doi: 10.1111/cge.13487. Epub 2018 Dec 21.
35	Amelogenesis Imperfecta: 1 Family, 2 Phenotypes, and 2 Mutated Genes.J Dent Res. 2016 Dec;95(13):1457-1463. doi: 10.1177/0022034516663200. Epub 2016 Aug 24.
36	TMEM165 deficiency causes a congenital disorder of glycosylation. Am J Hum Genet. 2012 Jul 13;91(1):15-26. doi: 10.1016/j.ajhg.2012.05.002. Epub 2012 Jun 7.