The Experts below are selected from a list of 300 Experts worldwide ranked by ideXlab platform
A Richiericosta - One of the best experts on this subject based on the ideXlab platform.
-
urinary tract involvement in EEC Syndrome a clinical study in 25 brazilian patients
American Journal of Medical Genetics, 1992Co-Authors: Aguinaldo C Nardi, Ubirajara Ferreira, Nelson Rodrigues Netto, Luis Alberto Magna, E S O Rodini, A RichiericostaAbstract:We have evaluated 25 patients (14 isolated and 11 familial cases) with the EEC Syndrome for genitourinary (GU) tract anomalies through intravenous pyelogram (IVP), voiding urethrocystography, and sonographic examination. Fifty-two percent of the patients (7 isolated and 6 familial cases) had involvement of the urinary tract, with no significant difference between isolated and familial cases. The present data seem to reflect the best estimate of the prevalence of genitourinary anomalies in patients with the EEC Syndrome. © 1992 Wiley-Liss, Inc.
-
EEC Syndrome report on 20 new patients clinical and genetic considerations
American Journal of Medical Genetics, 1990Co-Authors: E S O Rodini, A RichiericostaAbstract:We report on 20 Brazilian patients (11 sporadic and 9 familial cases) with the ectrodactyly, ectodermal dysplasia, clefting Syndrome (EEC Syndrome). Genetic aspects, clinical manifestations, and differential diagnosis of the Syndromes involving ectodermal dysplasia/limb anomalies and cleft lip/palate are discussed.
Yoshimitsu Fukushima - One of the best experts on this subject based on the ideXlab platform.
-
EEC Syndrome ectrodactyly ectodermal dysplasia and cleft lip palate with a balanced reciprocal translocation between 7q11 21 and 9p12 or 7p11 2 and 9q12 in three generations
Clinical Genetics, 2008Co-Authors: Tomonobu Hasegawa, Shinji Asamura, Makoto Ninomiya, Yukihiro Hasegawa, Toshiro Nagai, Yutaka Tsuchiya, Yoshimitsu FukushimaAbstract:: Familial cases (a grandfather, a father and a daughter) of the EEC Syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) are reported. All of them have a balanced reciprocal translocation (46,XY or XX, t(7;9) (q11.21;p12) or (46,XY or XX, t(7;9) (p11.2;q12)), but no other members of the family have either the EEC Syndrome or chromosome abnormalities. This indicates that one of the chromosome sites 7q11.21, 9p12, 7p11.2 and 9q12 is a candidate for gene locus of the EEC Syndrome.
-
EEC Syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) with a balanced reciprocal translocation between 7q11.21 and 9p12 (or 7p11.2 and 9q12) in three generations.
Clinical Genetics, 2008Co-Authors: Tomonobu Hasegawa, Shinji Asamura, Makoto Ninomiya, Yukihiro Hasegawa, Toshiro Nagai, Yutaka Tsuchiya, Yoshimitsu FukushimaAbstract:: Familial cases (a grandfather, a father and a daughter) of the EEC Syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) are reported. All of them have a balanced reciprocal translocation (46,XY or XX, t(7;9) (q11.21;p12) or (46,XY or XX, t(7;9) (p11.2;q12)), but no other members of the family have either the EEC Syndrome or chromosome abnormalities. This indicates that one of the chromosome sites 7q11.21, 9p12, 7p11.2 and 9q12 is a candidate for gene locus of the EEC Syndrome.
-
EEC Syndrome type 3 with a heterozygous germline mutation in the p63 gene and b cell lymphoma
American Journal of Medical Genetics Part A, 2003Co-Authors: M Keiko D Akahoshi, Satoru Sakazume, Kenjiro Kosaki, Hirofumi Ohashi, Yoshimitsu FukushimaAbstract:Lines of evidence have recently indicated a relationship between mutations in the P63 gene and ectrodactyly-ectodermal dysplasia-clefting (EEC) Syndrome type 3 (EEC3). The p63 gene (P63) has homology to P53 known as a tumor-suppressor gene, but biological function of its protein has not yet been known well. There have been two reported patients who had EEC Syndrome associated with malignant lymphoma. However, they did not undergo sequencing analysis of P63. Here, we present with a Japanese girl who had EEC3 and developed diffuse large B-cell type non-Hodgkin lymphoma. In this patient, we documented a heterozygous germline mutation, Asp312Gly, in P63. We speculated that p63 may exert a biological function as a tumor suppressor. Malignant lymphoma should be considered as an important complication of EEC3. © 2003 Wiley-Liss, Inc.
-
EEC Syndrome type 3 with a heterozygous germline mutation in the P63 gene and B cell lymphoma.
American journal of medical genetics. Part A, 2003Co-Authors: Keiko Akahoshi, Kenjiro Kosaki, Satoru Sakazume, Hirofumi Ohashi, Yoshimitsu FukushimaAbstract:Lines of evidence have recently indicated a relationship between mutations in the P63 gene and ectrodactyly-ectodermal dysplasia-clefting (EEC) Syndrome type 3 (EEC3). The p63 gene (P63) has homology to P53 known as a tumor-suppressor gene, but biological function of its protein has not yet been known well. There have been two reported patients who had EEC Syndrome associated with malignant lymphoma. However, they did not undergo sequencing analysis of P63. Here, we present with a Japanese girl who had EEC3 and developed diffuse large B-cell type non-Hodgkin lymphoma. In this patient, we documented a heterozygous germline mutation, Asp312Gly, in P63. We speculated that p63 may exert a biological function as a tumor suppressor. Malignant lymphoma should be considered as an important complication of EEC3.
Hans Van Bokhoven - One of the best experts on this subject based on the ideXlab platform.
-
EEC Syndrome arg227gln tp63 mutation and micturition difficulties is there a genotype phenotype correlation
American Journal of Medical Genetics Part A, 2007Co-Authors: Kenneth N Maclean, Hans Van Bokhoven, Stephen A Holme, Elizabeth Gilmour, Mark Taylor, Heide Scheffer, Nicole Graf, Grahame H H Smith, Ella Onikul, Celia MossAbstract:We report on two unrelated families with EEC Syndrome (ectrodactyly, ectodermal dysplasia, cleft lip/palate), each with an Arg227Gln TP63 gene mutation, where the phenotype overlapped extensively with the allelic disorder, limb-mammary Syndrome (LMS). Features common to both families were an ectodermal dysplasia principally affecting tooth, breast and nipple development, dacryostenosis and severe micturition difficulties. Additional findings included post-axial digital hypoplasia, cleft uvula, anal stenosis, hypoplasia of the perineal body and biopsy-proven interstitial cystitis. No individual had cleft lip. Split hand-split foot malformation (SHFM) occurred in one child-born after the molecular diagnosis was established. Unlike previous reports, the urinary symptoms were refractory to treatment with oral Fibrase and persisted into adulthood. Of the six cases/families now reported with EEC Syndrome and Arg227Gln TP63 mutation, four have manifested this distinct urological abnormality, indicative of a genotype-phenotype correlation.
-
p63 gene mutations in EEC Syndrome limb mammary Syndrome and isolated split hand split foot malformation suggest a genotype phenotype correlation
American Journal of Human Genetics, 2001Co-Authors: Hans Van Bokhoven, Pascal H G Duijf, Ben C J Hamel, Michael J Bamshad, Eugenio Sangiorgi, Fiorella Gurrieri, Kaate R J Vanmolkot, Ellen Van Beusekom, Sylvia E C Van Beersum, Jacopo CelliAbstract:p63 mutations have been associated with EEC Syndrome (ectrodactyly, ectodermal dysplasia, and cleft lip/palate), as well as with nonsyndromic split hand–split foot malformation (SHFM). We performed p63 mutation analysis in a sample of 43 individuals and families affected with EEC Syndrome, in 35 individuals affected with SHFM, and in three families with the EEC-like condition limb-mammary Syndrome (LMS), which is characterized by ectrodactyly, cleft palate, and mammary-gland abnormalities. The results differed for these three conditions. p63 gene mutations were detected in almost all (40/43) individuals affected with EEC Syndrome. Apart from a frameshift mutation in exon 13, all other EEC mutations were missense, predominantly involving codons 204, 227, 279, 280, and 304. In contrast, p63 mutations were detected in only a small proportion (4/35) of patients with isolated SHFM. p63 mutations in SHFM included three novel mutations: a missense mutation (K193E), a nonsense mutation (Q634X), and a mutation in the 3′ splice site for exon 5. The fourth SHFM mutation (R280H) in this series was also found in a patient with classical EEC Syndrome, suggesting partial overlap between the EEC and SHFM mutational spectra. The original family with LMS (van Bokhoven et al. 1999) had no detectable p63 mutation, although it clearly localizes to the p63 locus in 3q27. In two other small kindreds affected with LMS, frameshift mutations were detected in exons 13 and 14, respectively. The combined data show that p63 is the major gene for EEC Syndrome, and that it makes a modest contribution to SHFM. There appears to be a genotype-phenotype correlation, in that there is a specific pattern of missense mutations in EEC Syndrome that are not generally found in SHFM or LMS.
Joost Schalkwijk - One of the best experts on this subject based on the ideXlab platform.
-
apr 246 prima 1 met rescues epidermal differentiation in skin keratinocytes derived from EEC Syndrome patients with p63 mutations
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Jinfeng Shen, Ellen H Van Den Bogaard, Evelyn N Kouwenhoven, Vladimir J N Bykov, Tuula Rinne, Qiang Zhang, Geuranne S Tjabringa, Christian Gilissen, Simon J Van Heeringen, Joost SchalkwijkAbstract:p53 and p63 share extensive sequence and structure homology. p53 is frequently mutated in cancer, whereas mutations in p63 cause developmental disorders manifested in ectodermal dysplasia, limb defects, and orofacial clefting. We have established primary adult skin keratinocytes from ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) Syndrome patients with p63 mutations as an in vitro human model to study the disease mechanism in the skin of EEC patients. We show that these patient keratinocytes cultured either in submerged 2D cultures or in 3D skin equivalents have impaired epidermal differentiation and stratification. Treatment of these patient keratinocytes with the mutant p53-targeting compound APR-246/PRIMA-1MET (p53 reactivation and induction of massive apoptosis) that has been successfully tested in a phase I/II clinical trial in cancer patients partially but consistently rescued morphological features and gene expression during epidermal stratification in both 2D and 3D models. This rescue coincides with restoration of p63 target-gene expression. Our data show that EEC patient keratinocytes with p63 mutations can be used for characterization of the abnormal molecular circuitry in patient skin and may open possibilities for the design of novel pharmacological treatment strategies for patients with mutant p63-associated developmental abnormalities.
-
APR-246/PRIMA-1 MET rescues epidermal differentiation in skin keratinocytes derived from EEC Syndrome patients with p63 mutations
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Jinfeng Shen, Ellen H Van Den Bogaard, Evelyn N Kouwenhoven, Vladimir J N Bykov, Tuula Rinne, Qiang Zhang, Geuranne S Tjabringa, Christian Gilissen, Simon J Van Heeringen, Joost SchalkwijkAbstract:p53 and p63 share extensive sequence and structure homology. p53 is frequently mutated in cancer, whereas mutations in p63 cause developmental disorders manifested in ectodermal dysplasia, limb defects, and orofacial clefting. We have established primary adult skin keratinocytes from ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) Syndrome patients with p63 mutations as an in vitro human model to study the disease mechanism in the skin of EEC patients. We show that these patient keratinocytes cultured either in submerged 2D cultures or in 3D skin equivalents have impaired epidermal differentiation and stratification. Treatment of these patient keratinocytes with the mutant p53-targeting compound APR-246/PRIMA-1MET (p53 reactivation and induction of massive apoptosis) that has been successfully tested in a phase I/II clinical trial in cancer patients partially but consistently rescued morphological features and gene expression during epidermal stratification in both 2D and 3D models. This rescue coincides with restoration of p63 target-gene expression. Our data show that EEC patient keratinocytes with p63 mutations can be used for characterization of the abnormal molecular circuitry in patient skin and may open possibilities for the design of novel pharmacological treatment strategies for patients with mutant p63-associated developmental abnormalities.
Richard J.h. Smith - One of the best experts on this subject based on the ideXlab platform.
-
split hand split foot malformation associated with sensorineural deafness inner and middle ear malformation hypodontia congenital vertical talus and deletion of eight microsatellite markers in 7q21 1 q21 3
Journal of Medical Genetics, 2001Co-Authors: E Haberlandt, Judith Loffler, Almut Hirststadlmann, Bernd Stockl, Peter Heinzerian, Werner Judmaier, Gerd Utermann, H Fischer, Thomas Muller, Richard J.h. SmithAbstract:Editor—The split hand/split foot malformation (SHFM, MIM 183600) is a central reduction defect of the hands and feet and occurs both as an isolated malformation and as part of several Syndromes including the EEC Syndrome (MIM 129900). We report on a 2 year old boy with SHFM associated with features of ectodermal hypoplasia, a submucous cleft palate, congenital vertical talus, malformations of the middle ear, profound sensorineural hearing loss resulting from Mondini dysplasia, and a de novo deletion of the paternal chromosome 7q21.1-q21.3. This patient with syndromic SHFM represents a case of atypical EEC Syndrome, but also displays abnormalities previously not associated with SHFM or EEC Syndrome. The classical features of the autosomal dominant inherited EEC Syndrome are ectrodactyly, ectodermal dysplasia, and clefting of the lip/palate. In most patients, there are additional anomalies typically affecting the urogenital and lacrimal systems.1 2 Some patients also have dysmorphic facies, a tendency to infectious disease, endocrine disorders, and mental retardation. This phenotypic variability has become increasingly apparent over the last 15 years3 4 and numerous related and overlapping Syndromes have been delineated by many investigators.5 In an attempt to clarify classification, major and minor criteria for the diagnosis of EEC Syndrome have been elaborated.3 4 Dominant inheritance of EEC has been documented in several large multigenerational families.6 At least 15 patients have been reported to have cytogenetic abnormalities of chromosome 7q21.2-7q22.1, including nine patients with interstitial deletions.7-9 In addition, mutations in the gene encoding the transactivation factor p63 on chromosome 3q27 have been identified in familial and sporadic cases of EEC Syndrome.10 A third locus was mapped to chromosome 19q,11 further delineating the genetic heterogeneity of this Syndrome. The reason for the phenotypic heterogeneity in EEC Syndrome patients with 7q abnormalities is unclear …
-
Split hand/split foot malformation associated with sensorineural deafness, inner and middle ear malformation, hypodontia, congenital vertical talus, and deletion of eight microsatellite markers in 7q21.1-q21.3
Journal of Medical Genetics, 2001Co-Authors: E Haberlandt, Judith Loffler, Bernd Stockl, Werner Judmaier, Gerd Utermann, H Fischer, Thomas Muller, Almut Hirst-stadlmann, Peter Heinz-erian, Richard J.h. SmithAbstract:Editor—The split hand/split foot malformation (SHFM, MIM 183600) is a central reduction defect of the hands and feet and occurs both as an isolated malformation and as part of several Syndromes including the EEC Syndrome (MIM 129900). We report on a 2 year old boy with SHFM associated with features of ectodermal hypoplasia, a submucous cleft palate, congenital vertical talus, malformations of the middle ear, profound sensorineural hearing loss resulting from Mondini dysplasia, and a de novo deletion of the paternal chromosome 7q21.1-q21.3. This patient with syndromic SHFM represents a case of atypical EEC Syndrome, but also displays abnormalities previously not associated with SHFM or EEC Syndrome. The classical features of the autosomal dominant inherited EEC Syndrome are ectrodactyly, ectodermal dysplasia, and clefting of the lip/palate. In most patients, there are additional anomalies typically affecting the urogenital and lacrimal systems.1 2 Some patients also have dysmorphic facies, a tendency to infectious disease, endocrine disorders, and mental retardation. This phenotypic variability has become increasingly apparent over the last 15 years3 4 and numerous related and overlapping Syndromes have been delineated by many investigators.5 In an attempt to clarify classification, major and minor criteria for the diagnosis of EEC Syndrome have been elaborated.3 4 Dominant inheritance of EEC has been documented in several large multigenerational families.6 At least 15 patients have been reported to have cytogenetic abnormalities of chromosome 7q21.2-7q22.1, including nine patients with interstitial deletions.7-9 In addition, mutations in the gene encoding the transactivation factor p63 on chromosome 3q27 have been identified in familial and sporadic cases of EEC Syndrome.10 A third locus was mapped to chromosome 19q,11 further delineating the genetic heterogeneity of this Syndrome. The reason for the phenotypic heterogeneity in EEC Syndrome patients with 7q abnormalities is unclear …