Amelogenesis Imperfecta via the C4orf26 Gene
- Summary and Pricing
- Clinical Features and Genetics
|Test Code||Test Copy Genes||Individual Gene Price||CPT Code Copy CPT Codes|
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The great majority of tests are completed within 18 days.
AI and AI-related syndromes are currently known to be caused by mutations in the following genes: AMELX (Aldred et al. 1992), DLX3 (Price et al. 1998), ENAM (Mardh et al. 2002), KLK4 (Hart et al. 2004), MMP20 (Kim et al. 2005), FAM83H (Lee et al. 2008; Kim et al. 2008), WDR72 (El-Sayed et al. 2009), FAM20A (O'Sullivan et al. 2011), C4orf26 (Parry et al. 2012), ROGDI (Schossig et al. 2012), SLC24A4 (Parry et al. 2013), ITGB6 (Poulter et al. 2013; Wang et al. 2013), LAMB3 (Kim et al. 2013), CNNM4 (Parry et al. 2009) and NHS (Burdon et al. 2003).
Enamel defects can also occur as syndrome disorders. For example, Kohlschütter–Tönz syndrome features enamel defects, psychomotor delay or regression and seizures caused by ROGDI mutations (Tucci et al. 2013); Nance-Horan syndrome (NHS) is characterized by congenital cataracts, dental anomalies, dysmorphic features and mental retardation caused by mutations in the NHS gene (Burdon et al. 2003); Jalili Syndrome features autosomal-Recessive Cone-Rod dystrophy and amelogenesis Imperfecta caused by mutations in the CNNM4 gene (Parry et al. 2009); and mutations in the FAM20A gene cause amelogenesis imperfecta and gingival hyperplasia syndrome as well as amelogenesis imperfecta and renal syndrome (O’Sullivan et al. 2011; Wang et al. 2013).
Indications for Test
|Official Gene Symbol||OMIM ID|
|Amelogenesis imperfecta, hypomaturation type, IIA4||614832|
- Genetic Counselor Team - email@example.com
- Juan Dong, PhD, FACMG - firstname.lastname@example.org
- Aldred MJ, Crawford PJ, Roberts E, Thomas NS. 1992. Identification of a nonsense mutation in the amelogenin gene (AMELX) in a family with X-linked amelogenesis imperfecta (AIH1). Hum. Genet. 90: 413–416. PubMed ID: 1483698
- Burdon KP, McKay JD, Sale MM, Russell-Eggitt IM, Mackey DA, Wirth MG, Elder JE, Nicoll A, Clarke MP, FitzGerald LM, Stankovich JM, Shaw MA, et al. 2003. Mutations in a Novel Gene, NHS, Cause the Pleiotropic Effects of Nance-Horan Syndrome, Including Severe Congenital Cataract, Dental Anomalies, and Mental Retardation. Am J Hum Genet 73: 1120–1130. PubMed ID: 14564667
- Crawford PJ, Aldred M, Bloch-Zupan A. 2007. Amelogenesis imperfecta. Orphanet Journal of Rare Diseases 2: 17. PubMed ID: 17408482
- El-Sayed W, Parry DA, Shore RC, Ahmed M, Jafri H, Rashid Y, Al-Bahlani S, Harasi S Al, Kirkham J, Inglehearn CF, Mighell AJ. 2009. Mutations in the Beta Propeller WDR72 Cause Autosomal-Recessive Hypomaturation Amelogenesis Imperfecta. The American Journal of Human Genetics 85: 699–705. PubMed ID: 19853237
- Hart PS. 2004. Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. Journal of Medical Genetics 41: 545–549. PubMed ID: 15235027
- Human Gene Mutation Database (Bio-base).
- Kim J, Simmer J, Hart T, Hart P, Ramaswami M, Bartlett J, Hu J. 2005. MMP-20 mutation in autosomal recessive pigmented hypomaturation amelogenesis imperfecta. J Med Genet 42: 271–275. PubMed ID: 15744043
- Kim J-W, Lee S-K, Lee ZH, Park J-C, Lee K-E, Lee M-H, Park J-T, Seo B-M, Hu JC-C, Simmer JP. 2008. FAM83H Mutations in Families with Autosomal-Dominant Hypocalcified Amelogenesis Imperfecta. The American Journal of Human Genetics 82: 489–494. PubMed ID: 18252228
- Kim JW, Seymen F, Lee KE, Ko J, Yildirim M, Tuna EB, Gencay K, Shin TJ, Kyun HK, Simmer JP, Hu JC-C. 2013. LAMB3 mutations causing autosomal-dominant amelogenesis imperfecta. J. Dent. Res. 92: 899–904. PubMed ID: 23958762
- Lee S-K, Hu JC-C, Bartlett JD, Lee K-E, Lin BP-J, Simmer JP, Kim J-W. 2008. Mutational Spectrum of FAM83H: The C-Terminal Portion is Required for Tooth Enamel Calcification. Hum Mutat 29: E95–E99. PubMed ID: 18484629
- Mårdh CK, Bäckman B, Holmgren G, Hu JC-C, Simmer JP, Forsman-Semb K. 2002. A nonsense mutation in the enamelin gene causes local hypoplastic autosomal dominant amelogenesis imperfecta (AIH2). Hum. Mol. Genet. 11: 1069–1074. PubMed ID: 11978766
- O’Sullivan J, Bitu CC, Daly SB, Urquhart JE, Barron MJ, Bhaskar SS, Martelli-Junior H, Santos Neto PE dos, Mansilla MA, Murray JC, Coletta RD, Black GCM, et al. 2011. Whole-Exome Sequencing Identifies FAM20A Mutations as a Cause of Amelogenesis Imperfecta and Gingival Hyperplasia Syndrome. Am J Hum Genet 88: 616–620. PubMed ID: 21549343
- Parry DA, Brookes SJ, Logan CV, Poulter JA, El-Sayed W, Al-Bahlani S, Harasi S Al, Sayed J, Raïf EM, Shore RC, Dashash M, Barron M, et al. 2012. Mutations in C4orf26, Encoding a Peptide with In Vitro Hydroxyapatite Crystal Nucleation and Growth Activity, Cause Amelogenesis Imperfecta. The American Journal of Human Genetics 91: 565–571. PubMed ID: 22901946
- Parry DA, Mighell AJ, El-Sayed W, Shore RC, Jalili IK, Dollfus H, Bloch-Zupan A, Carlos R, Carr IM, Downey LM, Blain KM, Mansfield DC, et al. 2009. Mutations in CNNM4 Cause Jalili Syndrome, Consisting of Autosomal-Recessive Cone-Rod Dystrophy and Amelogenesis Imperfecta. Am J Hum Genet 84: 266–273. PubMed ID: 19200525
- Parry DA, Poulter JA, Logan CV, Brookes SJ, Jafri H, Ferguson CH, Anwari BM, Rashid Y, Zhao H, Johnson CA, Inglehearn CF, Mighell AJ. 2013. Identification of Mutations in SLC24A4, Encoding a Potassium-Dependent Sodium/Calcium Exchanger, as a Cause of Amelogenesis Imperfecta. The American Journal of Human Genetics 92: 307–312. PubMed ID: 23375655
- Poulter JA, Brookes SJ, Shore RC, Smith CEL, Farraj L Abi, Kirkham J, Inglehearn CF, Mighell AJ. 2013. A missense mutation in ITGB6 causes pitted hypomineralized amelogenesis imperfecta. Human Molecular Genetics. PubMed ID: 24319098
- Price JA, Wright JT, Kula K, Bowden DW, Hart TC. 1998. A common DLX3 gene mutation is responsible for tricho-dento-osseous syndrome in Virginia and North Carolina families. J Med Genet 35: 825–828. PubMed ID: 9783705
- Schossig A, Wolf NI, Fischer C, Fischer M, Stocker G, Pabinger S, Dander A, Steiner B, Tonz O, Kotzot D, Haberlandt E, Amberger A, et al. 2012. Mutations in ROGDI Cause Kohlschütter-Tönz Syndrome. Am J Hum Genet 90: 701–707. PubMed ID: 22424600
- Tucci A, Kara E, Schossig A, Wolf NI, Plagnol V, Fawcett K, Paisán-Ruiz C, Moore M, Hernandez D, Musumeci S. 2013. Kohlschütter–Tönz Syndrome: Mutations in ROGDI and Evidence of Genetic Heterogeneity. Human mutation 34: 296–300. PubMed ID: 23086778
- Wang S-K, Choi M, Richardson AS, Reid BM, Lin BP, Wang SJ, Kim J-W, Simmer JP, Hu JC-C. 2013. ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis imperfecta. Hum. Mol. Genet. ddt611. PubMed ID: 24305999
- Witkop CJ. 1988. Amelogenesis imperfecta, dentinogenesis imperfecta and dentin dysplasia revisited: problems in classification. Journal of Oral Pathology & Medicine 17: 547–553. PubMed ID: 3150442
Bi-Directional Sanger Sequencing
Nomenclature for sequence variants was from the Human Genome Variation Society (http://www.hgvs.org). As required, DNA is extracted from the patient specimen. PCR is used to amplify the indicated exons plus additional flanking non-coding sequence. After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit. Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer. In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions. In nearly all cases, the full coding region of each exon as well as 20 bases of non-coding DNA flanking the exon are sequenced.
As of March 2016, we compared 17.37 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 12 years of our lab operation we have Sanger sequenced roughly 8,800 PCR amplicons. Only one error has been identified, and this was due to sequence analysis error.
Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).
In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.
Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.
In most cases, only the indicated exons and roughly 20 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.
In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.
Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.
Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.
Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.
(Delivery accepted Monday - Saturday)
- Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
- For small babies, we require a minimum of 1 ml of blood.
- Only one blood tube is required for multiple tests.
- Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
- During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
- In cold weather, include an unfrozen ice pack in the shipping container as insulation.
- At room temperature, blood specimen is stable for up to 48 hours.
- If refrigerated, blood specimen is stable for up to one week.
- Label the tube with the patient name, date of birth and/or ID number.
(Delivery accepted Monday - Saturday)
- Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
- For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
- DNA may be shipped at room temperature.
- Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
- We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.
(Delivery preferred Monday - Thursday)
- PreventionGenetics should be notified in advance of arrival of a cell culture.
- Culture and send at least two T25 flasks of confluent cells.
- Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
- Send specimens in insulated, shatterproof container overnight.
- Cell cultures may be shipped at room temperature or refrigerated.
- Label the flasks with the patient name, date of birth, and/or ID number.
- We strongly recommend maintaining a local back-up culture. We do not culture cells.