Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.698
Filtrar
2.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 46(4): 163-166, oct.-dic. 2019. tab, graf, ilus
Artigo em Espanhol | IBECS | ID: ibc-184305

RESUMO

Los trastornos relacionados con mutaciones del gen IRF6, comprenden desde una afectación casi asintomática con la única presencia de hoyuelos labiales que son la manifestación más sutil del síndrome de van der Woude, hasta manifestaciones congénitas graves que incluyen anomalías faciales, musculoesqueléticas y genitourinarias que corresponden al síndrome de pterigium poplíteo. Pese a que existe cierta relación fenotipo-genotipo entre las mutaciones del gen IRF6, estas tienen una penetrancia incompleta y una expresión variable, inter e intrafamiliar


The disorders related to IRF6 encompass a spectrum from an almost asymptomatic affectation, with the only presence of isolated lip pits, which are a mild presentation of van der Woude syndrome, to the presence in the other extreme, of congenital manifestations that include facial anomalies, musculoskeletal and genitourinary malformations, corresponding to popliteal pterygium syndrome. Although there is a certain phenotype-genotype relationship between mutations of the IRF6 gene, such mutations have incomplete penetrance and variable inter-and intra-familial expression


Assuntos
Humanos , Feminino , Gravidez , Adulto , Anormalidades Múltiplas/diagnóstico , Fenda Labial/diagnóstico , Dedos/anormalidades , Sindactilia/diagnóstico , Mutação , Fenda Labial/genética , Deformidades Congênitas das Extremidades Inferiores/diagnóstico , Feto/anormalidades
3.
BMC Med Genet ; 20(1): 174, 2019 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706290

RESUMO

BACKGROUND: Polydactyly is one of the most common congenital hand/foot malformations in humans. Mutations in GLI3 have been reported to cause syndromic and non-syndromic forms of preaxial and postaxial polydactylies. CASE PRESENTATION: The patient was a 2-year-old boy who underwent surgery in our hospital. The right hand and left foot of the patient were labelled as postaxial polydactyly type B, and there was cutaneous webbing between the 3rd and 4th fingers of the left hand. We identified a novel c. 1622C > T variant in GLI3 leading to an isolated postaxial synpolydactyly. CONCLUSIONS: The patient carries a novel autosomal dominant heterozygous missense mutation. This mutation c.1622C > T;p.(Thr541Met) in the GLI3 gene may affect the normal function of the zinc finger domain (ZFD) in a different way. However, it seems that more research is needed to determine the exact effects of this mutation.


Assuntos
Dedos/anormalidades , Mutação de Sentido Incorreto , Proteínas do Tecido Nervoso/genética , Polidactilia/genética , Dedos do Pé/anormalidades , Proteína Gli3 com Dedos de Zinco/genética , Dedos de Zinco , Sequência de Aminoácidos , Pré-Escolar , Humanos , Masculino , Proteínas do Tecido Nervoso/química , Linhagem , Homologia de Sequência de Aminoácidos , Proteína Gli3 com Dedos de Zinco/química
4.
BMC Med Genet ; 20(1): 187, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752730

RESUMO

BACKGROUND: Cohen syndrome (CS) is an uncommon developmental disease with evident clinical heterogeneity. VPS13B is the only gene responsible for CS. Only few sporadic cases of CS have been reported in China. CASE PRESENTATION: A Chinese family with two offspring-patients affected by developmental delay and intellectual disability was investigated in this study. Exome sequencing was performed, and compound heterozygous mutations in VPS13B were segregated for family members with autosomal recessive disorder. Splicing mutation c.3666 + 1G > T (exon 24) and nonsense mutation c. 9844 A > T:p.K3282X (exon 54) were novel. We revisited the family and learned that both patients are affected by microcephaly, developmental delay, neutropenia, and myopia and have a friendly disposition, all of which are consistent with CS phenotypes. We also found that both patients have hyperlinear palms, which their parents do not have. VPS13B mutations reported among the Chinese population were reviewed accordingly. CONCLUSIONS: This study presents two novel VPS13B mutations in CS. The identification of hyperlinear palms in a family affected by CS expands the phenotype spectrum of CS.


Assuntos
Dedos/anormalidades , Mãos/patologia , Deficiência Intelectual/genética , Microcefalia/genética , Hipotonia Muscular/genética , Mutação , Miopia/genética , Obesidade/genética , Degeneração Retiniana/genética , Proteínas de Transporte Vesicular/genética , Criança , Pré-Escolar , China , Deficiências do Desenvolvimento/genética , Feminino , Testes Genéticos , Humanos , Masculino , Linhagem , Fenótipo
5.
Nature ; 574(7777): 249-253, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31578523

RESUMO

The integrity of the mammalian epidermis depends on a balance of proliferation and differentiation in the resident population of stem cells1. The kinase RIPK4 and the transcription factor IRF6 are mutated in severe developmental syndromes in humans, and mice lacking these genes display epidermal hyperproliferation and soft-tissue fusions that result in neonatal lethality2-5. Our understanding of how these genes control epidermal differentiation is incomplete. Here we show that the role of RIPK4 in mouse development requires its kinase activity; that RIPK4 and IRF6 expressed in the epidermis regulate the same biological processes; and that the phosphorylation of IRF6 at Ser413 and Ser424 primes IRF6 for activation. Using RNA sequencing (RNA-seq), histone chromatin immunoprecipitation followed by sequencing (ChIP-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) of skin in wild-type and IRF6-deficient mouse embryos, we define the transcriptional programs that are regulated by IRF6 during epidermal differentiation. IRF6 was enriched at bivalent promoters, and IRF6 deficiency caused defective expression of genes that are involved in the metabolism of lipids and the formation of tight junctions. Accordingly, the lipid composition of the stratum corneum of Irf6-/- skin was abnormal, culminating in a severe defect in the function of the epidermal barrier. Collectively, our results explain how RIPK4 and IRF6 function to ensure the integrity of the epidermis and provide mechanistic insights into why developmental syndromes that are characterized by orofacial, skin and genital abnormalities result when this axis goes awry.


Assuntos
Diferenciação Celular , Células Epidérmicas/citologia , Epiderme/fisiologia , Fatores Reguladores de Interferon/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Anormalidades Múltiplas/genética , Animais , Fenda Labial/genética , Fissura Palatina/genética , Cistos/genética , Embrião de Mamíferos/citologia , Embrião de Mamíferos/embriologia , Embrião de Mamíferos/metabolismo , Células Epidérmicas/metabolismo , Epiderme/embriologia , Anormalidades do Olho/genética , Feminino , Dedos/anormalidades , Regulação da Expressão Gênica , Fatores Reguladores de Interferon/deficiência , Fatores Reguladores de Interferon/genética , Joelho/anormalidades , Articulação do Joelho/anormalidades , Lábio/anormalidades , Metabolismo dos Lipídeos/genética , Deformidades Congênitas das Extremidades Inferiores/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Fosfosserina/metabolismo , Proteínas Serina-Treonina Quinases/genética , Sindactilia/genética , Anormalidades Urogenitais/genética
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 993-995, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598943

RESUMO

OBJECTIVE: To explore the genetic etiology of a pedigree affected with tricho-rhino-phalangeal syndrome. METHODS: Next-generation sequencing (NGS) using a gene panel for hereditary osteopathies was carried out for the proband. Suspected mutation was validated in the proband and her parents by Sanger sequencing. RESULTS: A heterozygous frameshift variation c.1995dupA (p.Gly666Argfs*20) of the TRPS1 gene was detected in the proband but not in her parents. CONCLUSION: The novel c.1995dupA (p.Gly666Argfs*20) mutation of the TRPS1 gene probably underlies the disease in the proband.


Assuntos
Proteínas de Ligação a DNA/genética , Dedos/anormalidades , Mutação da Fase de Leitura , Doenças do Cabelo/genética , Síndrome de Langer-Giedion/genética , Nariz/anormalidades , Fatores de Transcrição/genética , Feminino , Humanos , Linhagem
7.
Muscle Nerve ; 60(6): 752-757, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31509255

RESUMO

INTRODUCTION: Andersen-Tawil syndrome (ATS) is characterized by a triad of periodic paralysis, ventricular arrhythmias, and dysmorphism. However, patients often lack one or more of these features. METHODS: Clinical and neurophysiological features were reviewed of five members in two families with heterozygous mutations in KCNJ2 (R218Q and R67W). RESULTS: Only one patient had all features of the triad of ATS. One patient had low-set ears, and the others had minor anomalies. Bidirectional ventricular tachycardias were seen in two patients. Two patients (R67W) never had episodes of paralysis. The long exercise test was abnormal in three patients with episodes of paralysis, but normal in two without paralytic episodes. DISCUSSION: ATS patients without skeletal muscle symptoms can have normal neurophysiological examinations. They can show variability in phenotype or the severity of arrhythmias. Such variability among patients who share the same gene mutations may result in underdiagnosis of ATS.


Assuntos
Síndrome de Andersen/fisiopatologia , Adolescente , Síndrome de Andersen/genética , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/fisiopatologia , Eletrocardiografia , Eletromiografia , Teste de Esforço , Feminino , Dedos/anormalidades , Humanos , Masculino , Pessoa de Meia-Idade , Paralisia/genética , Paralisia/fisiopatologia , Fenótipo , Canais de Potássio Corretores do Fluxo de Internalização/genética , Taquicardia Ventricular/genética , Taquicardia Ventricular/fisiopatologia , Complexos Ventriculares Prematuros/genética , Complexos Ventriculares Prematuros/fisiopatologia , Adulto Jovem
8.
AJR Am J Roentgenol ; 213(3): 534-548, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31268729

RESUMO

OBJECTIVE. The purpose of this article is to review the general guidelines for MRI of the finger and emphasize normal finger anatomy as it relates to abnormalities and injuries. CONCLUSION. Advanced imaging, particularly MRI, is increasingly relied on to make the diagnosis and guide management of finger injuries. It is incumbent on radiologists to understand the complex anatomy of the fingers as well as to be familiar with common injuries and aspects of injuries that affect management in order to meaningfully contribute to patient care.


Assuntos
Traumatismos dos Dedos/diagnóstico por imagem , Dedos/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Dedos/anormalidades , Dedos/anatomia & histologia , Humanos
9.
Artigo em Inglês | MEDLINE | ID: mdl-31343132

RESUMO

Trichorhinophalangeal syndrome (TRPS) is rare genetic disorder with autosomal dominant inheritance. The TRPS1 gene is located on the long arm of the eighth chromosome (8q24.12). The phenotype is variable and presents a wide clinical spectrum. Most cases are characterised by thin, sparse scalp hair, distinctive facial dysmorphism, and various skeletal abnormalities, especially of the hands and feet. Characteristic facial features may include a "pear-shaped" nose, micrognathia, dental anomalies, prominent ears, elongated philtrum, and thin upper vermillion border. In most cases, affected individuals exhibit skeletal abnormalities including brachydactyly and clinodac-tyly, short metacarpals phalanges, short feet and metatarsals, and pectus carinatum and hip joint malformations. Additionally, patients may exhibit short stature. This report presents four cases of TRPS (three sporadic and one familial). Clinical presentation included typical facial features and vari-ous skeletal abnormalities. Some TRPS symptoms may mimic growth hormone deficiency and other endocrine disturbances. The aim of this article is to deliver TRPS symptomatology. The treatment of TRPS is symptomatic and supportive and requires the coordination of several specialists, including paediatricians, endocrinologists, orthopaedic surgeons, dermatologists, and medical rehabilitation and den-tal specialists. In some cases, recombinant growth hormone therapy may be necessary. Genetic counselling may be of benefit for affect-ed individuals and their families.


Assuntos
Dedos/anormalidades , Doenças do Cabelo/diagnóstico , Síndrome de Langer-Giedion/diagnóstico , Nariz/anormalidades , Adolescente , Criança , Pré-Escolar , Feminino , Dedos/patologia , Doenças do Cabelo/genética , Doenças do Cabelo/patologia , Doenças do Cabelo/terapia , Humanos , Síndrome de Langer-Giedion/genética , Síndrome de Langer-Giedion/patologia , Síndrome de Langer-Giedion/terapia , Masculino , Mutação , Nariz/patologia , Fenótipo , Polônia , Proteínas Repressoras/genética
10.
Plast Reconstr Surg ; 144(1): 149-154, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31246822

RESUMO

BACKGROUND: Conventional dogma suggests that the use of local anesthetic with epinephrine is contraindicated in the digits because of fear of ischemia and necrosis. Although several reports have refuted this notion, the precept is still propagated in many clinical forums. For many years, the authors have used lidocaine with epinephrine to perform removal of postaxial polydactyly in infants and have observed few complications and no cases of digital ischemia or necrosis. This investigation details the authors' outcomes with this anesthetic modality in neonates and supports the growing body of literature documenting the safety of using lidocaine with epinephrine in the digits. METHODS: A retrospective review of all infants younger than 6 months who underwent preaxial and postaxial polydactyly excision and removal of their sequelae of the hand or foot under local anesthesia, from 2011 to 2017, was completed. All demographic characteristics, frequency of complications, and descriptive statistics of the sample clinical group were documented. RESULTS: In the 215 patients who met inclusion criteria, a total of 402 procedures were performed. Mean follow-up was 19.9 months for 140 patients, or 264 procedures (65.7 percent). The total complication rate was 2.6 percent. There were two cases of minor bleeding, one wound dehiscence, and four surgical-site infections. CONCLUSIONS: In 402 procedures of surgical excision of polydactyly in infants, there were few short-term complications, none of which were necrosis or any vascular complication related to the use of epinephrine. The authors believe that, with the use of a low-dose epinephrine injection (1:200,000), the risk for digital infarction is low in this population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Epinefrina/efeitos adversos , Polidactilia/cirurgia , Vasoconstritores/efeitos adversos , Anestésicos Locais/administração & dosagem , Quimioterapia Combinada , Epinefrina/administração & dosagem , Feminino , Dedos/anormalidades , Dedos/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Bloqueio Nervoso/métodos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Dedos do Pé/anormalidades , Dedos do Pé/cirurgia , Vasoconstritores/administração & dosagem
12.
Eur J Med Genet ; 62(8): 103688, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152918

RESUMO

Mesoaxial synostotic syndactyly (MSSD) with phalangeal reduction is an uncommon congenital limb abnormality characterized by central osseous synostosis at a metacarpal level, mesoaxial reduction of the fingers, and preaxial cutaneous syndactyly in toes. In rare cases, the disease is also associated with fifth finger clinodactyly and postaxial polydactyly. It has autosomal recessive inheritance pattern caused by homozygous variants in the gene BHLHA9 mapped at chromosome 17p13.3. In the present study, a consanguineous family of Pakistani origin segregating MSSD in autosomal recessive form was characterized at clinical and genetic levels. Clinically, the diseased individuals have MSSD associated with clinodactyly and polydactyly. Homozygosity mapping followed by Sanger sequencing of BHLHA9 revealed a novel frameshift variant NM_001164405.1: c.409-409delC; p.(His137Thrfs*61) segregating with the disease phenotypes in the family. This is the second report providing evidence of association of polydactyly with MSSD caused by frameshift variant in the gene BHLHA9. The present molecular investigation will support genetic counselling of the local population carrying diseased variants.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Dedos/anormalidades , Polidactilia/genética , Sindactilia/genética , Sinostose/genética , Dedos do Pé/anormalidades , Feminino , Falanges dos Dedos da Mão/patologia , Dedos/fisiopatologia , Mutação da Fase de Leitura/genética , Humanos , Masculino , Linhagem , Polidactilia/complicações , Polidactilia/fisiopatologia , Sindactilia/complicações , Sindactilia/fisiopatologia , Sinostose/complicações , Sinostose/fisiopatologia , Dedos do Pé/fisiopatologia
14.
Hum Genet ; 138(6): 593-600, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30982135

RESUMO

Postaxial polydactyly (PAP) is a common limb malformation that often leads to cosmetic and functional complications. Molecular evaluation of polydactyly can serve as a tool to elucidate genetic and signaling pathways that regulate limb development, specifically, the anterior-posterior specification of the limb. To date, only five genes have been identified for nonsyndromic PAP: FAM92A, GLI1, GLI3, IQCE and ZNF141. In this study, two Pakistani multiplex consanguineous families with autosomal recessive nonsyndromic PAP were clinically and molecularly evaluated. From both pedigrees, a DNA sample from an affected member underwent exome sequencing. In each family, we identified a segregating frameshift (c.591dupA [p.(Q198Tfs*21)]) and nonsense variant (c.2173A > T [p.(K725*)]) in KIAA0825 (also known as C5orf36). Although KIAA0825 encodes a protein of unknown function, it has been demonstrated that its murine ortholog is expressed during limb development. Our data contribute to the establishment of a catalog of genes important in limb patterning, which can aid in diagnosis and obtaining a better understanding of the biology of polydactyly.


Assuntos
Dedos/anormalidades , Genes Recessivos/genética , Predisposição Genética para Doença/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação , Polidactilia/genética , Dedos do Pé/anormalidades , Animais , Consanguinidade , Saúde da Família , Feminino , Dedos/patologia , Genótipo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Linhagem , Fenótipo , Polidactilia/patologia , Dedos do Pé/patologia , Sequenciamento Completo do Exoma/métodos
15.
J Dtsch Dermatol Ges ; 17(4): 393-397, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30865379

RESUMO

Fibromatoses are a group of benign connective tissue tumors characterized by the infiltrative, aggressive proliferation of well-differentiated fibroblasts, leading to frequent local recurrence. Within this heterogeneous disease group, superficial fibromatoses show slower growth and more benign infiltration of surrounding tissues than deep fibromatoses. Superficial fibromatoses relevant to dermatology include palmar, plantar, and penile fibromatosis, knuckle pads, pachydermodactyly and infantile digital fibromatosis. They present clinically with subcutaneous nodules or cords that lead to local infiltration and limited mobility of the affected areas. Treatment options vary from watchful waiting, non-invasive methods such as radiotherapy and intralesional corticosteroid/collagenase injections to radical surgical procedures. Early intervention may disrupt disease progression and may even restore functional ability. These disorders should therefore be recognized and treated early in the course of the disease.


Assuntos
Fibroma/patologia , Dedos/patologia , Neoplasias de Tecido Conjuntivo/patologia , Adulto , Contratura de Dupuytren/epidemiologia , Contratura de Dupuytren/patologia , Diagnóstico Precoce , Feminino , Fibroma/congênito , Fibroma/epidemiologia , Fibroma/terapia , Fibromatose Plantar/epidemiologia , Fibromatose Plantar/patologia , Dedos/anormalidades , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Neoplasias Penianas/epidemiologia , Neoplasias Penianas/patologia , Tela Subcutânea/patologia , Conduta Expectante
16.
JAAPA ; 32(4): 32-37, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30913147

RESUMO

Although congenital hand anomalies associated with finger nubbins may be produced by amniotic band disruption sequence (ABDS), symbrachydactyly should be considered in the differential diagnosis. ABDS usually affects more than one limb but symbrachydactyly largely is limited to one upper extremity, and has five distinct clinical presentations: short-fingered, atypical cleft, monodactylous, peromelic, and a forearm proximal transverse deficiency. This article discusses the diagnosis of symbrachydactyly compared with ABDS and outlines plans for managing patients with symbrachydactyly.


Assuntos
Síndrome de Bandas Amnióticas , Dedos/anormalidades , Sindactilia/diagnóstico , Dedos do Pé/anormalidades , Feminino , Deformidades Congênitas da Mão/classificação , Humanos , Lactente , Radiografia , Sindactilia/etiologia , Sindactilia/patologia , Sindactilia/cirurgia
18.
Tech Hand Up Extrem Surg ; 23(2): 74-80, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30720566

RESUMO

The first toe-to-hand transplantation was done in 1898 by Nicoladoni. It was a staged procedure and the toe flap was based on a pedicle. With advancement of optical instruments and microsurgeons' skills in 1964 the first microvascular toe-to-hand transplantation on a rhesus monkey was done. The technique's development has not stopped, many authors have modified it to achieve better outcomes for both traumatic and congenital hand defects. The most commonly used toes for transplantation are first, second, and second to third toe block. Well described plantar and dorsal vascular systems for first web space vessels as well as possibility to perform successful perforator anastomosis allows us to improve toe-to-hand transplantation further. There is a paucity of studies on single fourth toe-to-hand transplantation. We performed fourth-toe transplantation for three pediatric patients (mean age, 73 mo) with congenital (n=2) and traumatic (n=1) hand defects. Common plantar digital arteries were used for blood supply to the transplanted toes. No vascular problems occurred, and all transplanted toes survived. Patients and parents are satisfied with functional and esthetic outcomes. Early podometry results show insignificant changes which should not harm the foot in the long-term. We believe the fourth-toe transplantation is a promising method to use to reconstruct congenital or traumatic absence of digits for pediatric population.


Assuntos
Traumatismos dos Dedos/cirurgia , Deformidades Congênitas da Mão/cirurgia , Procedimentos Ortopédicos/métodos , Dedos do Pé/transplante , Criança , Pré-Escolar , Contraindicações de Procedimentos , Feminino , Dedos/anormalidades , Dedos/cirurgia , Humanos , Masculino , Dedos do Pé/anatomia & histologia
19.
Mol Genet Metab ; 126(4): 504-512, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30691926

RESUMO

Mutations of the TRPS1 gene cause trichorhinophalangeal syndrome (TRPS), a skeletal dysplasia with dental abnormalities. TRPS dental phenotypes suggest that TRPS1 regulates multiple aspects of odontogenesis, including the tooth number and size. Previous studies delineating Trps1 expression throughout embryonic tooth development in mice detected strong Trps1 expression in dental mesenchyme, preodontoblasts, and dental follicles, suggesting that TRPS dental phenotypes result from abnormalities in early developmental processes. In this study, Trps1+/- and Trps1-/- mice were analyzed to determine consequences of Trps1 deficiency on odontogenesis. We focused on the aspects of tooth formation that are disturbed in TRPS and on potential molecular abnormalities underlying TRPS dental phenotypes. Microcomputed tomography analyses of molars were used to determine tooth size, crown shape, and mineralization of dental tissues. These analyses uncovered that disruption of one Trps1 allele is sufficient to impair mineralization of dentin in both male and female mice. Enamel mineral density was decreased only in males, while mineralization of the root dental tissues was decreased only in females. In addition, significantly smaller teeth were detected in Trps1+/- females. Histomorphometric analyses of tooth organs showed reduced anterior-posterior diameter in Trps1-/- mice. BrdU-incorporation assay detected reduced proliferation of mesenchymal and epithelial cells in Trps1-/- tooth organs. Immunohistochemistry for Runx2 and Osx osteogenic transcription factors revealed changes in their spatial distribution in Trps1-/- tooth organs and uncovered cell-type specific requirements of Trps1 for Osx expression. In conclusion, this study has demonstrated that Trps1 is a positive regulator of cell proliferation in both dental mesenchyme and epithelium, suggesting that the microdontia in TRPS is likely due to decreased cell proliferation in developing tooth organs. Furthermore, the reduced mineralization observed in Trps1+/- mice may provide some explanation for the extensive dental caries reported in TRPS patients.


Assuntos
Proliferação de Células , Fatores de Transcrição GATA/genética , Regulação da Expressão Gênica , Odontogênese , Calcificação de Dente , Alelos , Animais , Diferenciação Celular , Cárie Dentária/etiologia , Células Epiteliais , Feminino , Dedos/anormalidades , Doenças do Cabelo/complicações , Doenças do Cabelo/genética , Síndrome de Langer-Giedion/complicações , Síndrome de Langer-Giedion/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Dente Molar/patologia , Nariz/anormalidades , Microtomografia por Raio-X
20.
PLoS One ; 14(1): e0210097, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30629636

RESUMO

BACKGROUND: GLI2 encodes for a transcription factor that controls the expression of several genes in the Hedgehog pathway. Mutations in GLI2 have been described as causative of a spectrum of clinical phenotypes, notably holoprosencephaly, hypopituitarism and postaxial polydactyl. METHODS: In order to identify causative genetic variant, we performed exome sequencing of a trio from an Italian family with multiple affected individuals presenting clinical phenotypes in the Culler-Jones syndrome spectrum. We performed a series of cell-based assays to test the functional properties of mutant GLI2. RESULTS: Here we report a novel deletion c.3493delC (p.P1167LfsX52) in the C-terminal activation domain of GLI2. Functional assays confirmed the pathogenicity of the identified variant and revealed a dominant-negative effect of mutant GLI2 on Hedgehog signalling. CONCLUSIONS: Our results highlight the variable clinical manifestation of GLI2 mutations and emphasize the value of functional characterisation of novel gene variants to assist genetic counselling and diagnosis.


Assuntos
Anormalidades Craniofaciais/genética , Dedos/anormalidades , Proteínas Hedgehog/metabolismo , Hipopituitarismo/genética , Proteínas Nucleares/genética , Polidactilia/genética , Dedos do Pé/anormalidades , Proteína Gli2 com Dedos de Zinco/genética , Animais , Criança , Feminino , Mutação da Fase de Leitura , Células HEK293 , Hormônio do Crescimento Humano/deficiência , Humanos , Hipopituitarismo/congênito , Masculino , Camundongos , Células NIH 3T3 , Linhagem , Adeno-Hipófise/anormalidades , Transdução de Sinais/genética , Síndrome
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA