Description
Amelogenesis imperfecta eligibility statement:

Amelogenesis imperfecta inclusion criteria
Amelogenesis Imperfecta confirmed through clinical evaluation (including dental radiographs) by a specialist dentist with an interest in developmental enamel abnormalities.

Amelogenesis imperfecta exclusion criteria
Developmental enamel abnormalities attributable to other causes including Molar Incisor Hypomineralisation, iatrogenic causes (e.g. chemotherapy), severe systemic illness and fluorosis.

Prior genetic testing guidance
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Amelogenesis imperfecta prior genetic testing genes
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: Gene panel that includes AMELX, FAM83H, ENAM, c4orf26, KLK4, MMP20, WDR72, GPR68, LAMB3, LAMA3, ITGB4, COL17A1, LTBP3, FAM20A, FAM20C, DLX3, STIM1, LAMC2, PEX1, PEX6

Closing statement
These requirements will be kept under continual review during the main programme and may be subject to change.

5 reviewers

  • emma baple (Genomics England Curator)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Sarah Leigh (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Rebecca Foulger (Genomics England curator)

    Group: Other
    Workplace: Other

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Claire Smith (University of Leeds)

    Group: Other
    Workplace: Research lab

37 genes

37 reviewed, 26 green

List Gene Reviews Mode of inheritance Details
37 genes
Green Green List (high evidence)
ACP4
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Amelogenesis imperfecta, type IJ, 617297
  • hypoplastic amelogenesis imperfecta
Green Green List (high evidence)
AMBN
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amelogenesis imperfecta, type IF, 616270
Tags
  • cnv
Green Green List (high evidence)
AMELX
2 reviews
1 green
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis imperfecta, type 1E, 301200
  • Amelogenesis Imperfecta, Type IE, 301200
  • X-linked hypoplastic amelogenesis imperfecta
  • hypomaturation AI with variable hypoplastic foci
  • smooth hypoplastic AI
Tags
  • deletions
Green Green List (high evidence)
C4orf26
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis imperfecta, type IIA4, 614832
  • Amelogenesis Imperfecta, Type IIA4, 614832
  • hypomineralized amelogenesis imperfecta
Tags
  • new-gene-name
Green Green List (high evidence)
CNNM4
2 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
  • Emory Genetics Laboratory
Phenotypes
  • Jalili syndrome, 217080 (includes amelogenesis imperfecta)
  • cone-rod dystrophy and amelogenesis imperfecta
Green Green List (high evidence)
COL17A1
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Epidermolysis bullosa, junctional, non-Herlitz type, 226650 (includes enamel pitting)
  • Amelogenesis Imperfecta
  • non-Herlitz junctional epidermolysis bullosa (nH-JEB) and amelogenesis imperfecta
  • hypoplastic amelogenesis imperfecta
Tags
  • monogenic-polygenic
Green Green List (high evidence)
DLX3
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis imperfecta, type IV, 104510
  • Amelogenesis Imperfecta, Type IV, 104510
  • Amelogenesis Imperfecta, Dominant
  • amelogenesis imperfecta with taurodontism
  • Trichodontoosseous syndrome, 190320
  • Tricho-dento-osseous syndrome (TDO) (includes enamel hypoplasia)
  • hypoplastic AI, taurodontism and kinky hair
Green Green List (high evidence)
ENAM
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amelogenesis imperfecta, type IB, 104500
  • Amelogenesis imperfecta, type IC, 204650
  • Amelogenesis Imperfecta, Dominant
  • autosomal recessive amelogenesis imperfecta
Green Green List (high evidence)
FAM20A
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis imperfecta, type IG (enamel-renal syndrome), 204690
  • Amelogenesis Imperfecta, Type IG, 204690
  • Hypomieralised AI
Green Green List (high evidence)
FAM20C
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Raine Syndrome, 259775
  • hypoplastic Amelogenesis Imperfecta
Green Green List (high evidence)
FAM83H
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis imperfecta, type III, 130900
  • Amelogenesis Imperfecta, Type III, 130900
  • Hypocalcified AI
Green Green List (high evidence)
GPR68
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Amelogenesis imperfecta, hypomaturation type, IIA6, 617217
Tags
  • deletions
Green Green List (high evidence)
ITGB6
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Other
Phenotypes
  • amelogenesis imperfecta (non-syndromic form)
  • Amelogenesis imperfecta, type IH, 616221
  • Amelogenesis imperfecta, type IH, 616221
Green Green List (high evidence)
KLK4
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis imperfecta, type IIA1, 204700
  • Amelogenesis Imperfecta, Hypomaturation Type, IIA1, 204700
Green Green List (high evidence)
LAMA3
2 reviews
1 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis imperfecta, hypoplastic type
  • Epidermolysis bullosa, generalized atrophic benign 226650
  • Epidermolysis bullosa, junctional, Herlitz type 226700
  • Laryngoonychocutaneous syndrome 245660
Tags
  • monogenic-polygenic
Green Green List (high evidence)
LAMB3
2 reviews
1 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Amelogenesis imperfecta, type IA, 104530
  • Amelogenesis Imperfecta, Type IA, 104530
  • Epidermolysis bullosa, junctional, Herlitz type, 26700
  • Epidermolysis bullosa, junctional, non-Herlitz type, 226650
Green Green List (high evidence)
LTBP3
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Other
  • Expert Review Green
  • UKGTN
Phenotypes
  • Dental anomalies and short stature, 601216
  • Amelogenesis Imperfecta
  • syndromic AI with brachyolmia
Green Green List (high evidence)
MMP20
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis imperfecta, type IIA2, 612529
  • Amelogenesis Imperfecta, Hypomaturation Type, IIA2, 612529
  • Amelogenesis Imperfecta, Recessive
Green Green List (high evidence)
ORAI1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • UKGTN
  • Expert Review Green
Phenotypes
  • Immunodeficiency 9, 612782
Green Green List (high evidence)
PEX1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Heimler Syndrome 1, 234580 (includes amelogenesis imperfecta)
  • hypomineralized amelogenesis imperfecta
  • amelogenesis imperfecta
  • Peroxisomal Biogenesis Disorder 1A (NALD / IRD) 601539
  • Peroxisome biogenesis disorder 1A (Zellweger), 214100
Green Green List (high evidence)
PEX6
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Heimler Syndrome 2, 616617 (includes amelogenesis imperfecta)
  • Peroxisome biogenesis disorder 4A (Zellweger), 614862
  • Peroxisome biogenesis disorder 4B, 614863
Tags
  • watchlist
Green Green List (high evidence)
ROGDI
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Kohlschutter-Tonz syndrome, 226750
  • Amelogenesis imperfecta, hypocalcified type (primary and secondary teeth)
Green Green List (high evidence)
SLC13A5
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Expert Review Green
Phenotypes
  • Kohlschütter-Tönz syndrome(KTZS)
  • hypoplastic amelogenesis imperfecta
  • Epileptic encephalopathy, early infantile, 25 615905
Green Green List (high evidence)
SLC24A4
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Other
  • Expert Review Green
Phenotypes
  • amelogenesis imperfecta (non-syndromic form)
  • Amelogenesis imperfecta, type IIA5, 615887
  • hypomaturation/hypomineralised amelogenesis imperfecta
Green Green List (high evidence)
STIM1
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Immunodeficiency 10, 612783
Green Green List (high evidence)
WDR72
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
  • Expert Review Green
Phenotypes
  • Amelogenesis imperfecta, type IIA3, 613211
  • Amelogenesis Imperfecta, Type IIA3, 613211
  • Amelogenesis Imperfecta, Recessive
  • Hypomaturation AI
Amber Amber List (moderate evidence)
AMTN
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Literature
  • Expert Review Amber
Phenotypes
  • Amelogenesis imperfecta
  • dominant hypomineralised AI
  • Amelogenesis imperfecta, hypomaturation type
  • ?Amelogenesis imperfecta, type IIIB, 617607
Tags
  • watchlist
  • deletions
Amber Amber List (moderate evidence)
CLDN16
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis (FHHNC)
Amber Amber List (moderate evidence)
CLDN19
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Expert Review Amber
Phenotypes
  • Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis (FHHNC)
Amber Amber List (moderate evidence)
ITGB4
1 review
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis Imperfecta
  • Epidermolysis bullosa, junctional, with pyloric atresia, 226730 (includes Enamel hypoplasia)
  • Epidermolysis bullosa, junctional, non-Herlitz type, 226650 (includes enamel pitting)
Tags
  • watchlist
Amber Amber List (moderate evidence)
LAMC2
2 reviews
1 red
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis Imperfecta
  • Epidermolysis bullosa, junctional, Herlitz type, 226700
  • Epidermolysis bullosa, junctional, non-Herlitz type, 226650
Tags
  • watchlist
Amber Amber List (moderate evidence)
PEX26
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Peroxisome biogenesis disorder 7A (Zellweger), 614872
  • Peroxisome biogenesis disorder 7B, 614873
  • Heimler syndrome
  • Amelogenesis imperfecta
  • enamel dysplasia
Tags
  • watchlist
Red Red List (low evidence)
KCNJ1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
Phenotypes
  • Bartter syndrome, type 2, 241200
  • Amelogenesis Imperfecta
Red Red List (low evidence)
SMARCD2
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
Phenotypes
  • Specific granule deficiency 2, 617475
Red Red List (low evidence)
TMEM165
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
Phenotypes
  • amelogenesis imperfecta
Red Red List (low evidence)
TP63
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Literature
Phenotypes
  • Split hand-split foot-ectodermal dysplasia and amelogenesis imperfecta
Red Red List (low evidence)
TUFT1
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Other
Phenotypes
  • amelogenesis imperfecta

0 STRs

0 reviewed, 0 green

List STR Reviews Mode of inheritance Details
0 STRss

Major version comments

Downloads

Download lists

Download Version