Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of inherited defects of enamel formation. In isolated AI (no additional segregating features), mutations in at least 7 genes are known so far, causing dominant, recessive or X-linked AI and allowing the identification of the molecular etiology in 40–50% of affected families. We report on 2 siblings (an 11-year-old female and a 7-year-old male) born to consanguineous Turkish parents, with AI and mild, proportionate short stature. Both parents have normal teeth, but mother, maternal grandmother and great-grandfather are/were also of short stature. A spine X-ray performed in the girl excluded brachyolmia. Affymetrix GenomeWide SNP6.0 Array analysis identified no pathogenic copy number changes, but showed sharing of large homozygous regions, including chromosome band 15q21.3 containing the WDR72 gene. WDR72 sequence analysis in both siblings revealed homozygosity for a novel stop mutation in exon 10 (c.997A>T, p.Lys333X) explaining the AI phenotype. Mutations in WDR72 are a very rare cause of autosomal-recessive hypomaturation type of isolated AI. The mutation described in our patients specifies the diagnosis AI IIA3 and represents only the sixth WDR72 mutation reported so far. The WDR72 protein is critical for dental enamel formation, but its exact function is still unknown.

Keywords:
AI IIA3, Autosomal recessive amelogenesis imperfecta, Short stature, WDR72
1.
Aldred MJ, Savarirayan R, Crawford PJ: Amelogenesis imperfecta: a classification and catalogue for the 21st century. Oral Dis 9:19–23 (2003).
2.
Altug-Atac AT, Erdem D: Prevalence and distribution of dental anomalies in orthodontic patients. Am J Orthod Dentofacial Orthop 131:510–514 (2007).
3.
Bäckman B, Holm AK: Amelogenesis imperfecta: prevalence and incidence in a northern Swedish county. Community Dent Oral Epidemiol 14:43–47 (1986).
4.
Bailleul-Forestier I, Molla M, Verloes A, Berdal A: The genetic basis of inherited anomalies of the teeth. Part 1: clinical and molecular aspects of non-syndromic dental disorders. Eur J Med Genet 51:273–291 (2008a).
5.
Bailleul-Forestier I, Berdal A, Vinckier F, de Ravel T, Fryns JP, Verloes A: The genetic basis of inherited anomalies of the teeth. Part 2: syndromes with significant dental involvement. Eur J Med Genet 51:383–408 (2008b).
6.
Bertola DR, Antequera R, Rodovalho MJ, Honjo RS, Albano LM, et al: Brachyolmia with amelogenesis imperfecta: further evidence of a distinct entity. Am J Med Genet A 149A:532–534 (2009).
7.
Chan HC, Estrella NM, Milkovich RN, Kim JW, Simmer JP, Hu JC: Target gene analyses of 39 amelogenesis imperfecta kindreds. Eur J Oral Sci 119 Suppl 1:311–323 (2011).
8.
Cho SH, Seymen F, Lee KE, Lee SK, Kweon YS, et al: Novel FAM20A mutations in hypoplastic amelogenesis imperfecta. Hum Mutat 33:91–94 (2012).
9.
Chosack A, Eidelman E, Wisotski I, Cohen T: Amelogenesis imperfecta among Israeli Jews and the description of a new type of local hypoplastic autosomal recessive amelogenesis imperfecta. Oral Surg Oral Med Oral Pathol 47:148–156 (1979).
10.
Crawford PJ, Aldred M, Bloch-Zupan A: Amelogenesis imperfecta. Orphanet J Rare Dis 2:17 (2007).
11.
Dong J, Amor D, Aldred MJ, Gu T, Escamilla M, MacDougall M: DLX3 mutation associated with autosomal dominant amelogenesis imperfecta with taurodontism. Am J Med Genet A 133A:138–141 (2005).
12.
El-Sayed W, Parry DA, Shore RC, Ahmed M, Jafri H, et al: Mutations in the beta propeller WDR72 cause autosomal-recessive hypomaturation amelogenesis imperfecta. Am J Hum Genet 85:699–705 (2009).
13.
El-Sayed W, Shore RC, Parry DA, Inglehearn CF, Mighell AJ: Hypomaturation amelogenesis imperfecta due to WDR72 mutations: a novel mutation and ultrastructural analyses of deciduous teeth. Cells Tissues Organs 194:60–66 (2011).
14.
Gadhia K, McDonald S, Arkutu N, Malik K: Amelogenesis imperfecta: an introduction. Br Dent J 212:377–379 (2012).
15.
Gibson CW: The amelogenin proteins and enamel development in humans and mice. J Oral Biosci 53:248–256 (2011).
16.
Gupta SK, Saxena P, Jain S, Jain D: Prevalence and distribution of selected developmental dental anomalies in an Indian population. J Oral Sci 53:231–238 (2011).
17.
Hart PS, Hart TC, Michalec MD, Ryu OH, Simmons D, et al: Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. J Med Genet 41:545–549 (2004).
18.
Hart TC, Hart PS, Gorry MC, Michalec MD, Ryu OH, et al: Novel ENAM mutation responsible for autosomal recessive amelogenesis imperfecta and localised enamel defects. J Med Genet 40:900–906 (2003).
19.
Hu JC, Chun YH, Al Hazzazzi T, Simmer JP: Enamel formation and amelogenesis imperfecta. Cells Tissues Organs 186:78–85 (2007).
20.
Kim JW, Simmer JP, Hart TC, Hart PS, Ramaswami MD, et al: MMP-20 mutation in autosomal recessive pigmented hypomaturation amelogenesis imperfecta. J Med Genet 42:271–275 (2005).
21.
Kim JW, Lee SK, Lee ZH, Park JC, Lee KE, et al: FAM83H mutations in families with autosomal-dominant hypocalcified amelogenesis imperfecta. Am J Hum Genet 82:489–494 (2008).
22.
Lagerström M, Dahl N, Nakahori Y, Nakagome Y, Bäckman B, et al: A deletion in the amelogenin gene (AMG) causes X-linked amelogenesis imperfecta (AIH1). Genomics 10:971–975 (1991).
23.
Lee SK, Seymen F, Lee KE, Kang HY, Yildirim M, et al: Novel WDR72 mutation and cytoplasmic localization. J Dent Res 89:1378–1382 (2010).
24.
Mory A, Dagan E, Illi B, Duquesnoy P, Mordechai S, et al: A nonsense mutation in the human homolog of Drosophila rogdi causes Kohlschutter-Tonz syndrome. Am J Hum Genet 90:708–714 (2012).
25.
O’Sullivan J, Bitu CC, Daly SB, Urquhart JE, Barron MJ, et al: Whole-exome sequencing identifies FAM20A mutations as a cause of amelogenesis imperfecta and gingival hyperplasia syndrome. Am J Hum Genet 88:616–620 (2011).
26.
Parry DA, Mighell AJ, El-Sayed W, Shore RC, Jalili IK, et al: Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta. Am J Hum Genet 84:266–273 (2009).
27.
Rajpar MH, Harley K, Laing C, Davies RM, Dixon MJ: Mutation of the gene encoding the enamel-specific protein, enamelin, causes autosomal-dominant amelogenesis imperfecta. Hum Mol Genet 10:1673–1677 (2001).
28.
Schossig A, Wolf NI, Fischer C, Fischer M, Stocker G, et al: Mutations in ROGDI cause Kohlschütter-Tönz syndrome. Am J Hum Genet 90:701–707 (2012).
29.
Sedano HO: Congenital oral anomalies in Argentinian children. Community Dent Oral Epidemiol 3:61–63 (1975).
30.
Simmer JP, Papagerakis P, Smith CE, Fisher DC, Rountrey AN, et al: Regulation of dental enamel shape and hardness. J Dent Res 89:1024–1038 (2010).
31.
Verloes A, Jamblin P, Koulischer L, Bourguignon JP: A new form of skeletal dysplasia with amelogenesis imperfecta and platyspondyly. Clin Genet 49:2–5 (1996).
32.
Verloes A, Capri A, Gellé MP, van Wull W: Brachyolmia and amelogenesis imperfecta: a rare dento-osseous disorder. Abstract 22nd European Dysmorphology Meeting, Bischenberg, September 2011.
33.
Witkop CJ: Amelogenesis imperfecta, dentinogenesis imperfecta and dentin dysplasia revisited, problems in classification. J Oral Pathol 17:547–553 (1988).
34.
Witkop CJ, Sauk JJ: Heritable defects of enamel, in Stewart R, Prescott G (eds): Oral Facial Genetics, pp 151–226 (Mosby Company, St. Louis 1976).
35.
Wright JT, Torain M, Long K, Seow K, Crawford P, et al: Amelogenesis imperfecta: genotype-phenotype studies in 71 families. Cells Tissues Organs 194:279–283 (2011).
© 2012 S. Karger AG, Basel
2012
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.