BACKGROUND:Calcifying odontogenic cyst was described first by Gorlin et al. in 1962; since then several hundreds of cases had been reported. In 1981, Praetorius et al. proposed a widely used classification. Afterwards, several authors proposed different classifications and discussed its neoplastic potential. The 2005 WHO Classification of Odontogenic Tumours re-named this entity as calcifying cystic odontogenic tumour (CCOT) and defined the clinico-pathological features of the ghost cell odontogenic tumours, the CCOT, the dentinogenic ghost cell tumour (DGCT) and the ghost cell odontogenic carcinoma (GCOC).METHODS:The aim of this paper was to review the clinical-pathological features of 122 CCOT, DGCT and GCOC cases retrieved from the files of the oral pathology laboratories from 14 institutions in Mexico, South Africa, Denmark, the USA, Brazil, Guatemala and Peru. It attempts to clarify and to group the clinico-pathological features of the analysed cases and to propose an objective, comprehensive and useful classification under the 2005 WHO classification guidelines.RESULTS:CCOT cases were divided into four sub-types: (i) simple cystic; (ii) odontoma associated; (iii) ameloblastomatous proliferating; and (iv) CCOT associated with benign odontogenic tumours other than odontomas. DGCT was separated into a central aggressive DGCT and a peripheral non-aggressive counterpart. For GCOC, three variants were identified. The first reported cases of a recurrent peripheral CCOT and a multiple synchronous, CCOT are included.CONCLUSIONS:Our results suggest that ghost cell odontogenic tumours comprise a heterogeneous group of neoplasms which need further studies to define more precisely their biological behaviour.

SPONASTRIME dysplasia (SD) is an autosomal recessive skeletal dysplasia of the spondyloepimetaphyseal dysplasia (SEMD) type. The name was derived from "spondylar and nasal alterations with striated metaphyses" [Fanconi et al. 1983; Helv Paediat Acta 38: 267-280]. We follow two previously reported patients with SD [Patients 3, 4 in Langer et al. 1996; Am J Med Genet 63: 20-27]. Since the original publication, additional findings were identified in these patients.

When I received a phone call apprising me that I was the recipient of this august prize, I was, frankly, more than somewhat surprised. To date, I have written over 620 articles, 60 chapters, and have coauthored or edited 20 books, some of which have had Russian, Spanish, and Japanese translations—but the truth is that I am not a facile writer. I’ve always envied an author who puts pen to paper and out comes a nice, clean manuscript. I truly agonize over a sentence, and my way is definitely not the way textbooks should be written.

Regional skin hypoplasia has been described in several genetic syndromes, including focal dermal hypoplasia (FDH), microphthalmia with linear skin defects (MLS), oculocerebrocutaneous syndrome (OCCS), and terminal osseous dysplasia and pigmentary defects (TODP). All but OCCS have been reported to follow an X‐linked inheritance pattern. We describe a 14‐year‐old girl with clinical features overlapping with these disorders. She had mild mental retardation, macrocephaly, microphthalmia, right‐sided morning glory optic disc anomaly, palmar and lip pits, and polysyndactyly. A swirling pattern of skin hypopigmentation, papular hypopigmented and herniated skin lesions reminiscent of FDH most prominent over her face, head, hands, and feet was evident. Brain magnetic resonance imaging (MRI) showed polymicrogyria (most severely in the perisylvian and mesial frontal regions), enlarged left lateral ventricle, partial agenesis of the corpus callosum, and optic nerve tumor on the right. Dermatopathologic examination of the skin lesions was consistent with basaloid follicular hamartomas. The skin and digit anomalies observed overlap with FDH, but polymicrogyria, basaloid follicular hamartomas, optic nerve tumor, and morning glory anomaly have not previously been described in FDH. Skin defects in MLS are linear and the eyes typically have sclerocornea. Polymicrogyria has been described in OCCS, but not in any of the other three syndromes. The limb anomalies in TODP are reductions rather than polysyndactyly. Skin defects are localized to the face, and digital fibromas usually occur. While significant overlap exists between all four of the syndromes discussed, we believe that the constellation of anomalies observed in this girl most likely comprises a newly recognized syndrome. © 2003 Wiley‐Liss, Inc.

Lenz microphthalmia is inherited in an X-linked recessive pattern and comprises microphthalmia, mental retardation, and skeletal and other anomalies. Two loci associated with this syndrome, MAA (microphthalmia with associated anomalies) and MAA2 , are situated respectively at Xq27–q28 (refs. 1 , 2 ) and Xp11.4–p21.2 (ref. 3 ). We identified a substitution, nt 254C→T; P85L, in BCOR (encoding BCL-6-interacting corepressor, BCOR 4 ) in affected males from the family with Lenz syndrome previously used to identify the MAA2 locus 3 . Oculofaciocardiodental syndrome (OFCD; OMIM 300166) is inherited in an X-linked dominant pattern with presumed male lethality and comprises microphthalmia, congenital cataracts, radiculomegaly, and cardiac and digital abnormalities. Given their phenotypic overlap, we proposed that OFCD and MAA2 -associated Lenz microphthalmia were allelic, and we found different frameshift, deletion and nonsense mutations in BCOR in seven families affected with OFCD. Like wild-type BCOR, BCOR P85L and an OFCD-mutant form of BCOR can interact with BCL-6 and efficiently repress transcription. This indicates that these syndromes are likely to result from defects in alternative functions of BCOR, such as interactions with transcriptional partners other than BCL-6. We cloned the zebrafish ( Danio rerio ) ortholog of BCOR and found that knock-down of this ortholog caused developmental perturbations of the eye, skeleton and central nervous system consistent with the human syndromes, confirming that BCOR is a key transcriptional regulator during early embryogenesis.

Ekman-Westborg and Julin [1974: Oral Surg 38:217-222], described multiple macrodontia and multituberculism affecting the teeth without other anomalies (E-WJ). We describe a Chilean case in a 12-year-old with the typical dental alterations and with histopathologic findings that include absence of predentin layer and prominent reduced enamel epithelium. E-WJ is not a syndrome and we propose "multiple macrodontic multituberculism" as a better name for this anomaly of uncertain etiology affecting only the crowns of the teeth.

The original article to which this Erratum refers was published in Am J Med Genet 110:400–403.

WHIM syndrome is an immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia and extensive human papillomavirus (HPV) infection(1). Despite the peripheral neutropenia, bone marrow aspirates from affected individuals contain abundant mature myeloid cells, a condition termed myelokathexis(2). The susceptibility to HPV is disproportionate compared with other immunodeficiency conditions, suggesting that the product of the affected gene may be important in the natural control of this infection. We describe here the localization of the gene associated with WHIM syndrome to a region of roughly 12 cM on chromosome 2q21 and the identification of truncating mutations in the cytoplasmic tail domain of the gene encoding chemokine receptor 4 (CXCR4). Haplotype and mutation analyses in a pedigree transmitting myelokathexis as an apparently autosomal recessive trait support genetic heterogeneity for this aspect of the WHIM syndrome phenotype. Lymphoblastoid cell lines carrying a 19-residue truncation mutation show significantly greater calcium flux relative to control cell lines in response to the CXCR4 ligand, SDF-1, consistent with dysregulated signaling by the mutant receptor. The identification of mutations in CXCR4 in individuals with WHIM syndrome represents the first example of aberrant chemokine receptor function causing human disease and suggests that the receptor may be important in cell-mediated immunity to HPV infection.

The Robin sequence is a well-known cause of cleft palate and can be sporadic or familial, isolated or syndromic. We present a four-generation family with a lethal disorder inherited in an X-linked recessive pattern that includes Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistence of the left superior vena cava. We have designated this disorder "TARP" syndrome. All affected males die in infancy of unknown causes. An X-chromosome linkage scan was performed using 14 unaffected members of a single large family and 40 STRP markers. The gene was mapped to an 11-cM region in Xp11.23-q13.3. Markers DXS1003 and DXS8092 flank the region and three-point linkage analyses revealed a maximum LOD score of 2.75 at marker DXS1039. We have designated this locus as TARP. This locus was mapped without genotyping any affecteds and demonstrates that rare, lethal disorders can be evaluated by genetic linkage, even when no affected probands are available for study. Published 2003 Wiley-Liss, Inc.

Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. Filamin A, encoded by the gene FLNA , is a widely expressed protein that regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second messengers 1 , 2 . We identified localized mutations in FLNA that conserve the reading frame and lead to a broad range of congenital malformations, affecting craniofacial structures, skeleton, brain, viscera and urogenital tract, in four X-linked human disorders: otopalatodigital syndrome types 1 (OPD1; OMIM 311300) and 2 (OPD2; OMIM 304120), frontometaphyseal dysplasia (FMD; OMIM 305620) and Melnick–Needles syndrome (MNS; OMIM 309350). Several mutations are recurrent, and all are clustered into four regions of the gene: the actin-binding domain and rod domain repeats 3, 10 and 14/15. Our findings contrast with previous observations that loss of function of FLNA is embryonic lethal in males but manifests in females as a localized neuronal migration disorder, called periventricular nodular heterotopia (PVNH; refs. 3 – 6 ). The patterns of mutation, X-chromosome inactivation and phenotypic manifestations in the newly described mutations indicate that they have gain-of-function effects, implicating filamin A in signaling pathways that mediate organogenesis in multiple systems during embryonic development.

American Journal of Medical GeneticsVolume 112, Issue 3 p. 234-235 Commentary The language of the extremities Robert J. Gorlin, Corresponding Author Robert J. Gorlin gorli002@tc.umn.edu University of Minnesota School of Dentistry, Minneapolis, MinnesotaUniversity of Minnesota School of Dentistry, 515 Delaware Street S.E., 16-127, Minneapolis, MN 55455.Search for more papers by this author Robert J. Gorlin, Corresponding Author Robert J. Gorlin gorli002@tc.umn.edu University of Minnesota School of Dentistry, Minneapolis, MinnesotaUniversity of Minnesota School of Dentistry, 515 Delaware Street S.E., 16-127, Minneapolis, MN 55455.Search for more papers by this author First published: 25 September 2002 https://doi.org/10.1002/ajmg.10772Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume112, Issue315 October 2002Pages 234-235 RelatedInformation

American Journal of Medical GeneticsVolume 101, Issue 4 p. 290-291 Conference Report Asymmetry Robert J. Gorlin, Corresponding Author Robert J. Gorlin [email protected] Department of Oral Science, University of Minnesota Health Sciences Center, Minneapolis, MinnesotaDepartment of Oral Science, University of Minnesota Health Sciences Center, 515 Delaware Street S.E., 16-127, Minneapolis, Minnesota 55455.Search for more papers by this author Robert J. Gorlin, Corresponding Author Robert J. Gorlin [email protected] Department of Oral Science, University of Minnesota Health Sciences Center, Minneapolis, MinnesotaDepartment of Oral Science, University of Minnesota Health Sciences Center, 515 Delaware Street S.E., 16-127, Minneapolis, Minnesota 55455.Search for more papers by this author First published: 28 June 2001 https://doi.org/10.1002/ajmg.1222Citations: 6Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume101, Issue415 July 2001Pages 290-291 RelatedInformation

Abstract The craniosynostoses are etiologically and pathogenetically heterogeneous. Premature sutural fusion may occur alone or together with other anomalies, making up various syndromes. Over 90 syndromes are known. Several reviews are available (1–4), the most exhaustive review being that of Cohen and MacLean (4).

Abstract Rieger syndrome (hypodontia and primary mesodermal dysgenesis of the iris) Hypodontia in combination with malformation of part of the anterior chamber of the eye was described as early as 1883 by Vossius (43). However, the condition was not recognized as a heritable syndrome until the report of Rieger (34), in 1935. The syndrome has been expanded to include absent maxillary incisor teeth, malformations of the anterior chamber of the eye (Rieger anomaly), and umbilical anomalies (11,22,38). Its frequency has been estimated as 1/200,000 population (2).