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PURPOSE: The purpose of this study was to investigate pre-extraction variables associated with spontaneous space closure of the perma- nent second molar (PSM) following early extraction of the permanent first molar (PFM), and test an existing prediction model for the mandibular arch as the rates of spontaneous space closure are significantly lower in the mandible compared to the maxilla. METHODS: Pre-extraction panoramic radiographs of 162 patients (138 maxillary and 168 mandibular quadrants) between five and 15 years old at the time of PFM extraction were evaluated. The prediction model was applied to the mandibular quadrants. Postextraction radiographic evaluation was used for outcome assessment, with success defined as the presence of a visible contact between the second premolar and PSM without marginal ridge discrepancy. RESULTS: Success was observed in 82 percent of maxillary quadrants and 51 percent of mandibular quadrants. Maxillary PFM extraction between eight and 10 years or PSM Demirjian stage D or E demonstrated over 90 percent predictive probability for success. Mandibular PFM extraction at age eight years or PSM Demirjian stage D demonstrated 80 percent success. The prediction model did not add a more predictive value than chronological age or PSM Demirjian stage. CONCLUSIONS: The prediction model was not validated in this study population. Chronological age and permanent second molar developmental stage were the primary predictors for successful substitution with the permanent second molar.
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Diente Molar , Extracción Dental , Adolescente , Diente Premolar/diagnóstico por imagen , Diente Premolar/cirugía , Niño , Preescolar , Humanos , Mandíbula/diagnóstico por imagen , Diente Molar/diagnóstico por imagen , Diente Molar/cirugía , Radiografía PanorámicaRESUMEN
INTRODUCTION: Genetic and environmental etiologic factors have been described for maxillary canine impaction, except for the trabecular bone characteristics in the impacted area. The aim of this study was to evaluate the surface area and fractal dimension of the alveolar bone on cone-beam computed tomography (CBCT) images of patients with maxillary impacted canines. METHODS: The sample comprised preorthodontic treatment CBCT images of 49 participants with maxillary impacted canines (31 unilateral and 18 bilateral). CBCT images were acquired in portrait mode (17 × 23 cm high field of view) at 120 kV, 5 mA, 8.9-seconds exposure time, and 0.3-mm voxel size. Coronal slices (0.3 mm) were obtained from the right and left alveolar processes between the first and second maxillary premolars. We collected 64 × 64-pixel regions of interest between the premolars to assess maxillary bone area and fractal dimension using ImageJ software (National Institutes of Health, Bethesda, Md). Comparisons were made using paired t tests and linear regression. Repeated measurements were obtained randomly from about 20% of the sample. RESULTS: In subjects with unilateral impactions, the maxillary bone area (P = 0.0227) was higher in the impacted side, with a mean difference of 245.5 pixels (SD, 569.2), but the fractal dimension (P = 0.9822) was not, -0.0003 pixels (SD, 0.082). Comparisons of unilateral and bilateral subjects using a general linear mixed model test confirmed the increased bone area in the impacted side (P = 0.1062). The repeated measurements showed similar results. CONCLUSIONS: The maxillary alveolar bone area is increased in the impacted side compared with the nonimpacted side.
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Densidad Ósea , Tomografía Computarizada de Haz Cónico/métodos , Diente Canino/diagnóstico por imagen , Fractales , Maxilar/diagnóstico por imagen , Diente Impactado/diagnóstico por imagen , Femenino , Humanos , Masculino , Interpretación de Imagen Radiográfica Asistida por Computador , Estudios RetrospectivosRESUMEN
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital birth defects. NSCL/P is a complex multifactorial disease caused by interactions between multiple environmental and genetic factors. However, the causal single nucleotide polymorphism (SNP) signature profile underlying the risk of familial NSCL/P still remains unknown. We previously reported a 5.7-Mb genomic region on chromosome 18q21.1 locus that potentially contributes to autosomal dominant, low-penetrance inheritance of NSCL/P. In the current study, we performed exome sequencing on 12 familial genomes (six affected individuals, two obligate carriers, and four seemingly unaffected individuals) of a six-generation family to identify candidate SNPs associated with NSCL/P risk. Subsequently, targeted bidirectional DNA re-sequencing of polymerase chain reaction (PCR)-amplified high-risk regions of MYO5B gene and sequenom iPLEX genotpying of 29 candidate SNPs were performed on a larger set of 33 members of this NSCL/P family (10 affected + 4 obligate carriers + 19 unaffected relatives) to find SNPs significantly associated with NSCL/P trait. SNP vs. NSCL/P association analysis showed the MYO5B SNP rs183559995 GA genotype had an odds ratio of 18.09 (95% Confidence Interval = 1.86-176.34; gender-adjusted P = 0.0019) compared to the reference GG genotype. Additionally, the following SNPs were also found significantly associated with NSCL/P risk: rs1450425 (LOXHD1), rs6507992 (SKA1), rs78950893 (SMAD7), rs8097060, rs17713847 (SCARNA17), rs6507872 (CTIF), rs8091995 (CTIF), and rs17715416 (MYO5B). We could thus identify mutations in several genes as key candidate SNPs associated with the risk of NSCL/P in this large multi-generation family.
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PURPOSE: The purpose of this study was to compare the prevalence of dental anomalies in the primary and permanent dentition of patients with unilateral (UCLP) and bilateral (BCLP) cleft lip with or without palate. METHODS: One hundred two complete clinical records were randomly selected for review from a university-based cleft palate clinic. Only nonsyndromic UCLP and BCLP cases were further selected for analysis of dental anomalies. The prevalence of 9 dental categories, including anomalies in number, crown structure, position, and maxillary-mandibular relationship, was assessed and compared between UCLP and BCLP cases using Fisher's exact test. RESULTS: Of the 102 charts evaluated, there were 67 cases of UCLP and 29 cases of BCLP for a total of 96 cases. There was a high prevalence of dental anomalies in primary and permanent teeth; 93% of UCLP cases and 96% of BCLP cases presented with at least 1 dental anomaly. Significant differences ( P <.05) were only found in the prevalence of anodontia of a single tooth (UCLP=39%, BCLP=14%), multiple anodontia (UCLP=22%, BCLP=54%), and anterior malocclusion (UCLP=15%, BCLP=41%). CONCLUSIONS: There is a high prevalence of dental anomalies associated with orofacial clefts regardless of whether they are unilateral or bilateral cleft lip with or without palate.
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Labio Leporino/patología , Fisura del Paladar/patología , Anomalías Dentarias/epidemiología , Anomalías Dentarias/patología , Niño , Preescolar , Labio Leporino/epidemiología , Fisura del Paladar/epidemiología , Dentición Permanente , Femenino , Humanos , Masculino , Minnesota/epidemiología , Prevalencia , Diente PrimarioRESUMEN
The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood. We molecularly and functionally characterized one member of an evolutionarily dynamic gene family, plac8 onzin related protein 1 (ponzr1), in the zebrafish. ponzr1 mRNA is expressed early in the developing kidney and pharyngeal arches. Using ponzr1-targeting morpholinos, we show that ponzr1 is required for formation of the glomerulus. Loss of ponzr1 results in a nonfunctional glomerulus but retention of a functional pronephros, an arrangement similar to the aglomerular kidneys found in a subset of marine fish. ponzr1 is integrated into the pax2a pathway, with ponzr1 expression requiring pax2a gene function, and proper pax2a expression requiring normal ponzr1 expression. In addition to pronephric function, ponzr1 is required for pharyngeal arch formation. We functionally demonstrate that ponzr1 can act as a transcription factor or co-factor, providing the first molecular mode of action for this newly described gene family. Together, this work provides experimental evidence of an additional mechanism that incorporates evolutionarily dynamic, lineage-specific gene families into conserved regulatory gene networks to create functional organ diversity.
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Región Branquial/embriología , Pronefro/embriología , Factores de Transcripción/genética , Proteínas de Pez Cebra/genética , Pez Cebra/anatomía & histología , Pez Cebra/embriología , Pez Cebra/genética , Animales , Animales Modificados Genéticamente , Evolución Biológica , Biomarcadores/metabolismo , Región Branquial/metabolismo , Embrión no Mamífero/anatomía & histología , Embrión no Mamífero/fisiología , Regulación del Desarrollo de la Expresión Génica , Técnicas de Silenciamiento del Gen , Riñón/anatomía & histología , Morfogénesis/fisiología , Factor de Transcripción PAX2/genética , Factor de Transcripción PAX2/metabolismo , Fenotipo , Pronefro/metabolismo , Factores de Transcripción/metabolismo , Proteínas de Pez Cebra/metabolismoRESUMEN
OBJECTIVE: To determine the influence of landmark labeling on the accuracy and precision of an indirect facial anthropometric technique. MATERIALS AND METHODS: Eighteen standard linear craniofacial measurements were obtained from 10 adults using the 3dMDface system, with landmarks labeled (Labeled_3D) and without landmarks labeled (Unlabeled_3D) before image acquisition, and these were compared with direct anthropometry (Caliper). Images were acquired twice in two different sessions 1 week apart (T1 and T2). Accuracy and precision were determined by comparing mean measurement values and absolute differences between the three methods. RESULTS: Mean measurements derived from three-dimensional (3D) images and direct anthropologic measurements were mostly similar. However, statistically significant differences (P < .01) were noted for seven measurements in Labeled_3D and six measurements in Unlabeled_3D. The magnitudes of these differences were clinically insignificant (<2 mm). In terms of precision, results demonstrated good reproducibility for both methods, with a tendency toward more precise values in Labeled_3D, when compared with the other two techniques (P < .05). We found that Labeled_3D provided the most precise values, Unlabeled_3D produced less precise measurements, and Caliper was the least capable of generating precise values. CONCLUSIONS: Overall, soft tissue facial measurement with the 3dMDface system demonstrated similar accuracy and precision with traditional anthropometry, regardless of landmarking before image acquisition. Larger disagreements were found regarding measurements involving ears and soft tissue landmarks without distinct edges. The 3dMDface system demonstrated a high level of precision, especially when facial landmarks were labeled.
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Cefalometría/métodos , Cara/anatomía & histología , Imagenología Tridimensional/métodos , Adulto , Femenino , Marcadores Fiduciales , Humanos , Masculino , Fotogrametría , Reproducibilidad de los ResultadosRESUMEN
Robinow syndrome is a skeletal dysplasia with both autosomal dominant and autosomal recessive inheritance patterns. It is characterized by short stature, limb shortening, genital hypoplasia, and craniofacial abnormalities. The etiology of dominant Robinow syndrome is unknown; however, the phenotypically more severe autosomal recessive form of Robinow syndrome has been associated with mutations in the orphan tyrosine kinase receptor, ROR2, which has recently been identified as a putative WNT5A receptor. Here, we show that two different missense mutations in WNT5A, which result in amino acid substitutions of highly conserved cysteines, are associated with autosomal dominant Robinow syndrome. One mutation has been found in all living affected members of the original family described by Meinhard Robinow and another in a second unrelated patient. These missense mutations result in decreased WNT5A activity in functional assays of zebrafish and Xenopus development. This work suggests that a WNT5A/ROR2 signal transduction pathway is important in human craniofacial and skeletal development and that proper formation and growth of these structures is sensitive to variations in WNT5A function.
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Anomalías Múltiples/genética , Enfermedades del Desarrollo Óseo/genética , Desarrollo Embrionario/genética , Mutación Missense/genética , Proteínas Proto-Oncogénicas/genética , Transducción de Señal/genética , Proteínas Wnt/genética , Secuencia de Aminoácidos , Animales , Mapeo Cromosómico , Cruzamientos Genéticos , Cartilla de ADN/genética , Genes Dominantes/genética , Humanos , Hibridación in Situ , Ratones , Datos de Secuencia Molecular , Proteínas Proto-Oncogénicas/metabolismo , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/genética , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/metabolismo , Síndrome , Proteínas Wnt/metabolismo , Proteína Wnt-5a , Xenopus , Pez CebraRESUMEN
BACKGROUND: The current study was performed to describe frequencies and risk factors of altered oral health and odontogenesis in childhood cancer survivors. METHODS: In total, 9308 survivors who were diagnosed between 1970 and 1986 and 2951 siblings from the Childhood Cancer Survivor Study completed a survey that contained oral-dental health information. The authors analyzed treatment impact, socioeconomic data, and patient demographics on dental outcomes using univariate and multivariate logistic regression models to estimate odds ratios (ORs). RESULTS: In multivariate analysis, survivors were more likely to report microdontia (OR, 3.0; 95% confidence interval [95% CI], 2.4-3.8), hypodontia (OR, 1.7; 95% CI, 1.4-2.0), root abnormalities (OR, 3.0; 95% CI, 2.2-4.0), abnormal enamel (OR, 2.4; 95% CI, 2.0-2.9), teeth loss>or=6 (OR, 2.6; 95% CI, 1.9-3.6), severe gingivitis (OR, 1.2; 95% CI, 1.0-1.5), and xerostomia (OR, 9.7; 95% CI, 4.8-19.7). Controlling for chemotherapy and socioeconomic factors, radiation exposure of >or=20 Gray to dentition was associated significantly with an increased risk of >or=1 dental abnormality. Dose-dependent alkylating agent therapy significantly increased the risk of >or=1 anatomic/developmental dental abnormalities in survivors who were diagnosed at age<5 years (OR, 1.7, 2.7, and 3.3 for alkylating agent scores of 1, 2, and 3, respectively). CONCLUSIONS: Radiation and chemotherapy were independent risk factors for adverse oral-dental sequelae among childhood cancer survivors. The authors concluded that patients who received receiving alkylating agents at age<5 years should be closely monitored.
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Antineoplásicos/efectos adversos , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Radioterapia/efectos adversos , Enfermedades Dentales/inducido químicamente , Adulto , Edad de Inicio , Femenino , Humanos , Masculino , Odontogénesis/efectos de los fármacos , Odontogénesis/efectos de la radiación , Traumatismos por Radiación/epidemiología , Factores de Riesgo , Factores Socioeconómicos , Encuestas y Cuestionarios , Sobrevivientes/estadística & datos numéricos , Anomalías Dentarias/inducido químicamente , Enfermedades Dentales/epidemiologíaRESUMEN
PURPOSE: The purposes of this study were to: (1) quantify and compare permanent tooth development of cleft lip and palate (CLP) patients to age- and gender-matched controls; (2) relate these findings to cleft type and severity; and (3) examine delays in individual permanent maxillary teeth related to their proximity to the cleft. METHODS: Standardized methods using panoramic radiographs were employed to stage dental development and dental age for 49 children with clefts and 49 matched controls. Data were analyzed with a mixed linear model. RESULTS: Analyses indicated a correlation between delayed permanent tooth development and CLP with an overall delay of 0.52 years (P = .02) and with boys accounting for all the delay. No differences were found between subjects with unilateral or bilateral clefts. A nonsignificant trend was noted for greater delay in subjects with clefts of the primary and secondary palates vs primary palate alone. Teeth most often affected by the delay were maxillary first and second premolars and maxillary second molars. CONCLUSIONS: While permanent tooth development is delayed in cleft lip and palate patients, this delay is: found in boys only; is independent of the cleft type and severity; and is not correlated with proximity to the cleft.
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Labio Leporino/fisiopatología , Fisura del Paladar/fisiopatología , Odontogénesis/fisiología , Adolescente , Determinación de la Edad por los Dientes , Diente Premolar/diagnóstico por imagen , Diente Premolar/fisiopatología , Estudios de Casos y Controles , Niño , Labio Leporino/clasificación , Fisura del Paladar/clasificación , Femenino , Humanos , Masculino , Maxilar/diagnóstico por imagen , Diente Molar/diagnóstico por imagen , Diente Molar/fisiopatología , Radiografía Panorámica , Estudios Retrospectivos , Factores Sexuales , Factores de TiempoAsunto(s)
Anestésicos Locales/administración & dosificación , Iontoforesis , Lidocaína/administración & dosificación , Microinyecciones/instrumentación , Agujas , Analgesia por Acupuntura , Administración Cutánea , Anestesia Dental/instrumentación , Humanos , Inyecciones Intradérmicas/instrumentaciónRESUMEN
Recessive Robinow syndrome (RRS) is an extremely rare short stature genetic condition with significant and characteristic oral, dental, and facial attributes that generally requires coordinated multidisciplinary dental and medical interventions. This paper describes the clinical findings and dental management over the course of 4 years of a US-born Caucasian female with recessive Robinow syndrome who presented to our dental clinic at age 11 years, 0 months and who is now age 15 years, 3 months. Of special interest was the extent to which the patient's hyperplastic gingival tissues impeded both normal tooth eruption and orthodontic tooth movement.
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Anomalías Múltiples/patología , Enfermedades del Desarrollo Óseo/patología , Atención Dental para Enfermos Crónicos , Hiperplasia Gingival/complicaciones , Anomalías Maxilofaciales/patología , Adolescente , Cromosomas Humanos Par 9 , Femenino , Genes Recesivos , Hiperplasia Gingival/patología , Gingivectomía , Humanos , Deformidades Congénitas de las Extremidades/patología , Ortodoncia Correctiva , Síndrome , Erupción Dental , Diente Impactado/etiologíaAsunto(s)
Anomalías Dentarias/epidemiología , Anodoncia/epidemiología , Anodoncia/etnología , Asia Sudoriental/epidemiología , Asia Sudoriental/etnología , Dens in Dente/epidemiología , Dens in Dente/etnología , Esmalte Dental/anomalías , Dientes Fusionados/epidemiología , Dientes Fusionados/etnología , Humanos , Minnesota/epidemiología , Prevalencia , Estudios Retrospectivos , Anomalías Dentarias/etnología , Corona del Diente/anomalías , Diente Supernumerario/epidemiología , Diente Supernumerario/etnologíaRESUMEN
Periodic fever syndrome is composed of a group of disorders that present with recurrent predictable episodes of fever, which may be accompanied by: (1) lymphadenopathy; (2) malaise; (3) gastrointestinal disturbances; (4) arthrolgia; (5) stomatitis; and (6) skin lesions. These signs and symptoms occur in distinct intervals every 4 to 6 weeks and resolve without any residual effect, and the patient remains healthy between attacks. The evaluation must exclude: (1) infections; (2) neoplasms; and (3) autoimmune conditions. The purpose of this paper is to report the case of a 41/2- year-old white female who presented with a history of periodic fevers accompanied by: (1) joint pain; (2) skin lesions; (3) rhinitis; (4) vomiting; (5) diarrhea; and (6) an unusual asymptomatic, marked, fiery red glossitis with features evolving to resemble geographic tongue and then resolving completely between episodes. This may represent the first known reported case in the literature of a periodic fever syndrome presenting with such unusual recurring oral findings.
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Fiebre de Origen Desconocido/complicaciones , Glositis Migratoria Benigna/etiología , Glositis/etiología , Periodicidad , Artralgia/etiología , Preescolar , Femenino , Glositis/patología , Glositis Migratoria Benigna/patología , Humanos , Estomatitis Aftosa/etiología , SíndromeRESUMEN
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital facial defects, with an incidence of 1 in 700-1,000 live births among individuals of European descent. Several linkage and association studies of NSCL/P have suggested numerous candidate genes and genomic regions. A genomewide linkage analysis of a large multigenerational family (UR410) with NSCL/P was performed using a single-nucleotide-polymorphism array. Nonparametric linkage (NPL) analysis provided significant evidence of linkage for marker rs728683 on chromosome 18q21.1 (NPL=43.33 and P=.000061; nonparametric LOD=3.97 and P=.00001). Parametric linkage analysis with a dominant mode of inheritance and reduced penetrance resulted in a maximum LOD score of 3.61 at position 47.4 Mb on chromosome 18q21.1. Haplotype analysis with informative crossovers defined a 5.7-Mb genomic region spanned by proximal marker rs1824683 (42,403,918 bp) and distal marker rs768206 (48,132,862 bp). Thus, a novel genomic region on 18q21.1 was identified that most likely harbors a high-risk variant for NSCL/P in this family; we propose to name this locus "OFC11" (orofacial cleft 11).
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Cromosomas Humanos Par 18/genética , Labio Leporino/genética , Fisura del Paladar/genética , Ligamiento Genético , Genómica , Humanos , Escala de Lod , Linaje , Polimorfismo GenéticoRESUMEN
Morpholino phosphorodiamidate antisense oligonucleotides (MOs) and short interfering RNAs (siRNAs) are commonly used platforms to study gene function by sequence-specific knockdown. Both technologies, however, can elicit undesirable off-target effects. We have used several model genes to study these effects in detail in the zebrafish, Danio rerio. Using the zebrafish embryo as a template, correct and mistargeting effects are readily discernible through direct comparison of MO-injected animals with well-studied mutants. We show here indistinguishable off-targeting effects for both maternal and zygotic mRNAs and for both translational and splice-site targeting MOs. The major off-targeting effect is mediated through p53 activation, as detected through the transferase-mediated dUTP nick end labeling assay, acridine orange, and p21 transcriptional activation assays. Concurrent knockdown of p53 specifically ameliorates the cell death induced by MO off-targeting. Importantly, reversal of p53-dependent cell death by p53 knockdown does not affect specific loss of gene function, such as the cell death caused by loss of function of chordin. Interestingly, quantitative reverse-transcriptase PCR, microarrays and whole-mount in situ hybridization assays show that MO off-targeting effects are accompanied by diagnostic transcription of an N-terminal truncated p53 isoform that uses a recently recognized internal p53 promoter. We show here that MO off-targeting results in induction of a p53-dependent cell death pathway. p53 activation has also recently been shown to be an unspecified off-target effect of siRNAs. Both commonly used knockdown technologies can thus induce secondary but sequence-specific p53 activation. p53 inhibition could potentially be applicable to other systems to suppress off-target effects caused by other knockdown technologies.
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Técnicas Genéticas , Activación Transcripcional , Proteína p53 Supresora de Tumor/genética , Pez Cebra/genética , Animales , Apoptosis/efectos de los fármacos , Artefactos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Embrión no Mamífero/citología , Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/embriología , Embrión no Mamífero/metabolismo , Desarrollo Embrionario/efectos de los fármacos , Desarrollo Embrionario/genética , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Morfolinas/farmacología , Morfolinos , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fenotipo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Sensibilidad y Especificidad , Especificidad por Sustrato , Factores de Tiempo , Proteína p53 Supresora de Tumor/química , Proteína p53 Supresora de Tumor/metabolismo , Pez Cebra/embriologíaRESUMEN
Nonsyndromic cleft lip with or without cleft palate (CL-P) is a common congenital anomaly with incidence ranging from 1 in 300 to 1 in 2,500 live births. We analyzed two Indian pedigrees (UR017 and UR019) with isolated, nonsyndromic CL-P, in which the anomaly segregates as an autosomal dominant trait. The phenotype was variable, ranging from unilateral to bilateral CL-P. A genomewide linkage scan that used approximately 10,000 SNPs was performed. Nonparametric linkage (NPL) analysis identified 11 genomic regions (NPL>3.5; P<.005) that could potentially harbor CL-P susceptibility variations. Among those, the most significant evidence was for chromosome 13q33.1-34 at marker rs1830756 (NPL=5.57; P=.00024). This was also supported by parametric linkage; MOD score (LOD scores maximized over genetic model parameters) analysis favored an autosomal dominant model. The maximum LOD score was 4.45, and heterogeneity LOD was 4.45 (alpha =100%). Haplotype analysis with informative crossovers enabled the mapping of the CL-P locus to a region of approximately 20.17 cM (7.42 Mb) between SNPs rs951095 and rs726455. Thus, we have identified a novel genomic region on 13q33.1-34 that harbors a high-risk variant for CL-P in these Indian families.
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Cromosomas Humanos Par 13/genética , Labio Leporino/genética , Fisura del Paladar/genética , Ligamiento Genético , Genoma Humano , Haplotipos , Humanos , India , Linaje , Mapeo Físico de CromosomaRESUMEN
Cleft lip with or without cleft palate is a common birth defect affecting 1 in every 700 live births. Several genetic loci are believed to be involved in the pathogenesis of syndromic and non-syndromic clefting. We identified a pericentric inversion of chromosome 4, inv(4)(p13q21) that segregates with cleft lip in a two-generation family. By using a combination of fluorescence in situ hybridization, yeast artificial chromosome, bacterial artificial chromosome contig mapping, and database searching we mapped and sequenced the inversion breakpoint region. The pericentric inversion disrupts a gene (ACOD4) on chromosome 4q21 that codes for a novel acyl-CoA desaturase enzyme. The 3.0 kb human ACOD4 cDNA spans approximately 170 kb and is composed of five exons of ACOD4. The inversion breakpoint is located in the second exon. The 3.0 kb mRNA is expressed at high level in fetal brain; a lower expression level was found in fetal kidney. No expression of ACOD4 was detected in fetal lung or liver or in adult tissues. The five exons code for a protein of 330 amino acids, with a predicted molecular weight of 37.5 kDa. The protein is highly similar to acyl-CoA desaturases from Drosophila melanogaster to Homo sapiens. The catalytically essential histidine clusters and the potential transmembrane domains are well conserved.
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Inversión Cromosómica , Cromosomas Humanos Par 4/genética , Labio Leporino/genética , Reordenamiento Génico/genética , Secuencia de Aminoácidos , Línea Celular , Rotura Cromosómica/genética , Labio Leporino/enzimología , Labio Leporino/patología , Mapeo Contig , ADN/química , ADN/genética , Salud de la Familia , Ácido Graso Desaturasas/genética , Ácido Graso Desaturasas/metabolismo , Humanos , Recién Nacido , Masculino , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Homología de Secuencia de AminoácidoRESUMEN
PURPOSE: The purpose of this investigation was to evaluate the efficacy of a computerized injection device (Wand) on reducing pain behavior during injections with preschool-aged children. METHODS: Subjects consisted of 40 patients between the ages of 2 and 5 requiring local anesthesia for dental restorations in the maxilla. Patients were randomly assigned to either the Wand or the traditional anesthetic delivery system. A palatal approach to the anterior and middle superior alveolar nerves and the anterior superior alveolar nerve was used with the Wand injections. Buccal infiltration and palatal injections were used for the traditional method. Pain behavior was observed and coded. RESULTS: Results of Fisher Exact tests found that using the Wand to deliver anesthetic lead to significantly fewer (P < .01) disruptive behaviors in preschool-aged children when compared with a traditional injection regimen. In addition, none of the preschool-aged children exposed to the Wand required restraint during the initial interval, while nearly half of the children receiving a traditional injection required some type of immediate restraint. CONCLUSIONS: These results demonstrate that the Wand can significantly reduce disruptive behaviors in a population of young children who are traditionally more difficult to manage and may be one method of creating a more positive experience for the young child and the practitioner.