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Amelogenesis Imperfecta with Gingival Hyperplasia Syndrome and Amelogenesis Imperfecta with Renal Syndrome via the FAM20A Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11319 FAM20A 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11319FAM20A81479 81479(x2) $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Stela Berisha, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Amelogenesis imperfecta (AI) is a heterogeneous condition of enamel defects affecting both primary and permanent dentitions. Affected teeth are usually small, discolored, pitted or grooved, and prone to rapid wear and breakage. Based on clinical and radiographic features of the enamel defects as well as on the mode of inheritance pattern, AI has been divided into 14 different subtypes, which can be grouped into four major forms: hypoplastic, hypomaturation, hypocalcified, and hypomaturation-hypoplastic with taurodontism (Witkop et al. 1988). Hypoplastic AI shows reduced enamel volume with pits or grooves, but enamel is usually hard and translucent. Hypomaturation and hypocalcified AI have hypomineralized enamel with nearly normal matrix volume. Hypocalcified AI may present soft enamel which can be easily scraped away by attrition. Hypomaturation enamel is hard, but brittle and prone to breaking off. Hypomaturation-hypoplastic with taurodontism shows reduced, hypomineralized enamel with pits; in addition, molars or other teeth may present enlarged pulp chambers (Witkop et al. 1988; Crawford et al. 2007).

AI and AI-related syndrome 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).

Genetics

Mutations in the FAM20A gene cause autosomal recessive amelogenesis imperfecta with gingival fibromatosis syndrome and amelogenesis imperfecta with renal syndrome (O’Sullivan et al. 2011; Wang et al. 2013). The FAM20A protein coded by the FAM20A gene belongs to a protein kinase family that plays crucial roles in regulation of biomineralization process. FAM20A is expressed in ameloblasts, odontoblasts, and the parathyroid gland and is suggested to have roles in modulating biomineralization during enamel and blood vessel formation (Vogel et al. 2012). To date, more than 20 unique pathogenic variants have been reported. They are: 6 nonsense, 2 missense, 6 splicing, 11 small deletion and insertions (O’Sullivan et al. 2011; Wang et al. 2013; Kantaputra et al. 2013). Only one gross deletion of 79 base pairs was reported in a patient affected with amelogenesis imperfect with renal syndrome (Jaureguiberry et al. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

FAM20A mutations were identified in all 19 clinically diagnosed enamel renal syndrome cases from two studies (Wang et al, 2013; Jaureguiberry et al. 2013). Analytical sensitivity should be high, because almost all reported FAM20A mutations are point mutations or small deletions and duplications, which can be detected by sequencing. One large 79 base pair deletion has been reported (Jaureguiberry et al. 2013).

Testing Strategy

This test provides full coverage of all coding exons of the FAM20A gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with symptoms consistent with autosomal recessive hypoplastic amelogenesis imperfect, gingival fibromatosis, nephrocalcinosis and the family members of patients who have known FAM20A mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in FAM20A.

Gene

Official Gene Symbol OMIM ID
FAM20A 611062
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • 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).
  • Jaureguiberry G, Dure-Molla M De la, Parry D, Quentric M, Himmerkus N, Koike T, Poulter J, Klootwijk E, Robinette SL, Howie AJ, Patel V, Figueres M-L, et al. 2012. Nephrocalcinosis (Enamel Renal Syndrome) Caused by Autosomal Recessive  FAM20A  Mutations. Nephron Physiology 122: 1–6. PubMed ID: 23434854
  • Kantaputra PN, Kaewgahya M, Khemaleelakul U, Dejkhamron P, Sutthimethakorn S, Thongboonkerd V, Iamaroon A. 2014. Enamel-renal-gingival syndrome and FAM20A mutations. American Journal of Medical Genetics Part A 164: 1–9. PubMed ID: 24259279
  • 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
  • Vogel P, Hansen GM, Read RW, Vance RB, Thiel M, Liu J, Wronski TJ, Smith DD, Jeter-Jones S, Brommage R. 2012. Amelogenesis Imperfecta and Other Biomineralization Defects in Fam20a and Fam20c Null Mice. Veterinary Pathology 49: 998–1017. PubMed ID: 22732358
  • Wang S-K, Aref P, Hu Y, Milkovich RN, Simmer JP, El-Khateeb M, Daggag H, Baqain ZH, Hu JC-C. 2013. FAM20A Mutations Can Cause Enamel-Renal Syndrome (ERS). PLoS Genet 9: PubMed ID: 23468644
  • 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

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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1) Select Test Method (Backbone)


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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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