Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Neurocase ; 24(3): 140-144, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29969053

RESUMEN

Speech apraxia is a disorder of speech motor planning/programming leading to slow rate, articulatory distortion, and distorted sound substitutions. We describe the clinical profile evolution of a patient presenting with slowly progressive isolated speech apraxia that eventually led to the diagnosis of corticobasal syndrome (CBS), supporting the evidence that this rare speech disorder can be the first presentation of CBS. Moreover, we found a novel variant in MAPT gene, which is hypothesized to be disease-causing mutation. These results underscore the importance of genetic analysis - particularly in selected atypical cases - for in vivo understanding of possible pathophysiological disease process.


Asunto(s)
Apraxias/diagnóstico , Trastornos Parkinsonianos/diagnóstico , Trastornos del Habla/diagnóstico , Tauopatías/diagnóstico , Proteínas tau/genética , Anciano , Apraxias/etiología , Apraxias/genética , Humanos , Masculino , Trastornos Parkinsonianos/complicaciones , Trastornos Parkinsonianos/genética , Trastornos del Habla/etiología , Trastornos del Habla/genética , Tauopatías/complicaciones , Tauopatías/genética
2.
Am J Med Genet A ; 164A(1): 170-6, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24307393

RESUMEN

The identification of causes underlying intellectual disability (ID) is one of the most demanding challenges for clinical Geneticists and Researchers. Despite molecular diagnostics improvements, the vast majority of patients still remain without genetic diagnosis. Here, we report the results obtained using Whole Exome and Target Sequencing on nine patients affected by isolated ID without pathological copy number variations, which were accurately selected from an initial cohort of 236 patients. Three patterns of inheritance were used to search for: (1) de novo, (2) X-linked, and (3) autosomal recessive variants. In three of the nine proband-parent trios analyzed, we identified and validated two de novo and one X-linked potentially causative mutations located in three ID-related genes. We proposed three genes as ID candidate, carrying one de novo and three X-linked mutations. Overall, this systematic proband-parent trio approach using next generation sequencing could explain a consistent percentage of patients with isolated ID, thus increasing our knowledge on the molecular bases of this disease and opening new perspectives for a better diagnosis, counseling, and treatment.


Asunto(s)
Discapacidad Intelectual/genética , Biología Computacional , Exoma , Femenino , Genes Recesivos , Genes Ligados a X , Estudio de Asociación del Genoma Completo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Discapacidad Intelectual/diagnóstico , Cariotipo , Masculino , Mutación , Flujo de Trabajo
3.
Antibiotics (Basel) ; 13(7)2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39061358

RESUMEN

The stability of antibiotic preanalytical samples is a critical factor in therapeutic drug monitoring (TDM), a practice of undoubted importance for the proper therapeutic use of antibiotics, especially in complex management patients, such as pediatrics. This review aims to analyze the data in the literature regarding the preanalytical stability of some of the antibiotics for which TDM is most frequently requested. The literature regarding the preanalytical stability of amikacin, ampicillin, cefepime, ceftazidime, ciprofloxacin, daptomycin, gentamicin, levofloxacin, linezolid, meropenem, piperacillin, teicoplanin, and vancomycin in plasma, serum, whole blood, and dried blood/plasma spot samples was analyzed. Various storage temperatures (room temperature, 4 °C, -20 °C, and -80 °C) and various storage times (from 1 h up to 12 months) as well as subjecting to multiple freeze-thaw cycles were considered. The collected data showed that the non-beta-lactam antibiotics analyzed were generally stable under the normal storage conditions used in analytical laboratories. Beta-lactam antibiotics have more pronounced instability, particularly meropenem, piperacillin, cefepime, and ceftazidime. For this class of antibiotics, we suggest that storage at room temperature should be limited to a maximum of 4 h, storage at 2-8 °C should be limited to a maximum of 24 h, and storage at -20 °C should be limited to a maximum of 7 days; while, for longer storage, freezing at -80 °C is suggested.

4.
Front Endocrinol (Lausanne) ; 14: 1303989, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38107513

RESUMEN

Introduction: Girls with early thelarche may show an intermediate clinical picture between isolated premature thelarche (PT) and central precocious puberty (CPP), defined as "thelarche variant" (TV), characterized by an FSH-predominant response, although a univocal definition is lacking. Methods: Retrospective analysis on 91 girls with early thelarche (<8 years) and advanced bone age and/or accelerated growth who underwent 104 LHRH tests. Patients were classified into CPP (LH peak ≥5 IU/L; n = 28, 31%), TV (FSH peak ≥20 IU/L, LH peak <5 IU/L; n = 15, 16%), or PT (FSH peak <20 IU/L and LH peak <5 IU/L; n = 48, 53%). Results: TV patients were younger (5.51 years) and with less advanced bone age (+0.8 years). They had higher basal and peak FSH (2.5 and 26.6 IU/L) and lower basal and peak LH/FSH ratios (0.08 and 0.11). The prevalence of presence of ovarian follicles >5 mm in TV (42%) was similar to CPP but significantly higher than PT, whereas maximum ovarian volume was smaller in TV (1.0 cm3). At the last follow-up visit (available in 60% of the cases), 44% of TV developed CPP compared with 14% of PT (p = 0.04). At first evaluation, those who progressed to CPP had a higher basal FSH (3.2 IU/L), lower LH/FSH ratio (0.07), and a higher peak LH (4.1 IU/L) compared with those who did not progress to CPP (basal FSH 1.9 IU/L, p < 0.01; basal LH/FSH ratio 0.12, p < 0.01; peak LH 2.8 IU/L, p = 0.02). Conclusion: Using laboratory parameters only as a definition, we identified the clinical, laboratory, and imaging features of TV: these girls showed less advanced bone age and FSH predominance also at baseline, with smaller ovaries but with follicles >5 mm. Almost half of girls initially diagnosed as TV developed CPP at last follow-up visit, and these girls had higher baseline FSH, lower baseline LH/FSH ratio, and higher peak LH at first evaluation. Therefore, TV may represent a "precocious prepuberty" in which the FSH predominance may initially limit the progression into proper puberty, but it may eventually trigger full puberty (even CPP, depending on the girls' age).


Asunto(s)
Hormona Luteinizante , Pubertad Precoz , Femenino , Humanos , Lactante , Hormona Folículo Estimulante , Estudios Retrospectivos , Prevalencia , Pubertad Precoz/diagnóstico , Pubertad Precoz/epidemiología
5.
Am J Med Genet A ; 158A(4): 882-7, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22407795

RESUMEN

Deletion of the terminal part of long arm of chromosome 4 is a condition characterized by facial dysmorphisms, cardiac and limb defects, and developmental delay. Deletions usually involve the terminal part of the chromosome and most frequently are interstitial. Here, we report a de novo interstitial deletion resulting in a microdeletion of 6.9 Mb involving 4q31.3-q32.1 segment, detected by SNPs-Array technique in a 4-year-old female showing severe speech delay, mild facial dysmorphisms, and joint laxity. Phenotype-genotype relationships looking at the genes involved in this part of the chromosome were also carried out and data compared with those previously described.


Asunto(s)
Anomalías Múltiples/genética , Cromosomas Humanos Par 4/genética , Trastornos del Desarrollo del Lenguaje/genética , Eliminación de Secuencia/genética , Preescolar , Deleción Cromosómica , Discapacidades del Desarrollo/genética , Femenino , Genotipo , Humanos , Fenotipo
6.
Metabolites ; 12(12)2022 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-36557210

RESUMEN

Thiopurine drugs are part of the therapeutic armamentarium for pediatric patients suffering from inflammatory bowel disease (IBD) and acute lymphoblastic leukemia (ALL). The therapeutic drug monitoring of these drugs, consisting of measurements of the thiopurine metabolites thioguanine nucleotides (TGN) and methylmercaptopurine nucleotides (MMPN) are used to optimize the effectiveness of treatment and prevent adverse effects. In this context, we developed and validated a high-performance liquid chromatography-diode array detection (HPLC-DAD) method for the simultaneous quantification of thiopurine metabolites according to the most recent International Council for Harmonisation (ICH) guidelines. The calibration curves were built in the clinically relevant range of concentrations for TGN of 300-12,000 nM and for MMPN of 3000-60,000 nM. The limit of detection and the lower limit of quantification were 100 and 300 nM for TGN and 900 and 3000 nM for MMPN, respectively. The percentage of inter-day accuracy and precision (CV%) varied between 85 and 104% and 1.6 and 13.8%. Stability was demonstrated for both of the metabolites for at least 50 days at -20 °C. The proposed HPLC-DAD method showed an appropriate selectivity, specificity, linearity, accuracy, precision and good applicability to samples from patients with IBD and ALL undergoing thiopurine treatment.

7.
Mol Vis ; 17: 1662-8, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21738395

RESUMEN

PURPOSE: Usher syndrome is an autosomal recessive disorder characterized by hearing and vision loss. Usher syndrome is divided into three clinical subclasses (type 1, type 2, and type 3), which differ in terms of the severity and progression of hearing loss and the presence or absence of vestibular symptoms. Usher syndrome is defined by significant genetic heterogeneity, with at least 12 distinct loci described and 9 genes identified. This study aims to provide a molecular epidemiology report of Usher syndrome in Italy. METHODS: Molecular data have been obtained on 75 unrelated Italian patients using the most up-to date technology available for the screening of Usher syndrome gene mutations, i.e., the genotyping microarray developed by Asper Biotech (Tartu, Estonia), which simultaneously investigates 612 different marker positions using the well established arrayed primer extension methodology (APEX). RESULTS: Using this method, we found that 12% of cases (9 out of 75) harbored homozygous or compound heterozygous mutations in the gene positions analyzed, whereas 20% (15 out of 75) of the patients were characterized by the presence of only one mutated allele based on the positions analyzed. One patient was found to be compound heterozygous for mutations in two different genes and this represents an example of possible digenic inheritance in Usher syndrome. A total of 66.6% of cases (50 out of 75) were found to be completely negative for the presence of Usher syndrome gene mutations in the detected positions. Mutations detected by the array were confirmed by direct sequencing. CONCLUSIONS: These findings highlight the efficacy of the APEX-based genotyping approach in the molecular assessment of Usher patients, suggesting the presence of alleles not yet identified and/or the involvement of additional putative genes that may account for the pathogenesis of Usher syndrome.


Asunto(s)
Pérdida Auditiva/genética , Epidemiología Molecular/métodos , Síndromes de Usher/genética , Edad de Inicio , Alelos , Análisis Mutacional de ADN , Heterogeneidad Genética , Genotipo , Pérdida Auditiva/epidemiología , Pérdida Auditiva/patología , Heterocigoto , Homocigoto , Humanos , Italia , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Índice de Severidad de la Enfermedad , Síndromes de Usher/epidemiología , Síndromes de Usher/patología
8.
Mol Genet Genomic Med ; 8(1): e1056, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31851782

RESUMEN

BACKGROUND: Chromosomal microarray analysis (CMA) is nowadays widely used in the diagnostic path of patients with clinical phenotypes. However, there is no ascertained evidence to date on how to assemble single/combined clinical categories of developmental phenotypic findings to improve the array-based detection rate. METHODS: The Italian Society of Human Genetics coordinated a retrospective study which included CMA results of 5,110 Italian patients referred to 17 genetics laboratories for variable combined clinical phenotypes. RESULTS: Non-polymorphic copy number variants (CNVs) were identified in 1512 patients (30%) and 615 (32%) present in 552 patients (11%) were classified as pathogenic. CNVs were analysed according to type, size, inheritance pattern, distribution among chromosomes, and association to known syndromes. In addition, the evaluation of the detection rate of clinical subgroups of patients allowed to associate dysmorphisms and/or congenital malformations combined with any other single clinical sign to an increased detection rate, whereas non-syndromic neurodevelopmental signs and non-syndromic congenital malformations to a decreased detection rate. CONCLUSIONS: Our retrospective study resulted in confirming the high detection rate of CMA and indicated new clinical markers useful to optimize their inclusion in the diagnostic and rehabilitative path of patients with developmental phenotypes.


Asunto(s)
Aberraciones Cromosómicas , Discapacidades del Desarrollo/genética , Pruebas Genéticas/normas , Análisis de Secuencia por Matrices de Oligonucleótidos/normas , Guías de Práctica Clínica como Asunto , Variaciones en el Número de Copia de ADN , Discapacidades del Desarrollo/clasificación , Discapacidades del Desarrollo/diagnóstico , Pruebas Genéticas/métodos , Genética Médica/organización & administración , Humanos , Italia , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Fenotipo , Sensibilidad y Especificidad , Sociedades Médicas/normas
9.
Radiology ; 251(1): 280-6, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19190252

RESUMEN

PURPOSE: To measure epidermal thickness by using skin ultrasonography (US) in a series of healthy control subjects and obligate carriers for the worldwide most frequent form of congenital hearing loss owing to the mutated alleles of the connexin 26 gene (GJB2). MATERIALS AND METHODS: The patent for the protocol, coupled with a new sonographic probe specifically designed to analyze epidermal thickness and a dedicated algorithm to classify individuals in groups, is pending. Institutional ethics committee approval and patient consent were obtained. After a preliminary study in 23 subjects aimed to define the best body site and instrument and protocol for US, a total of 303 individuals (237 healthy subjects, 51 carriers, and 15 homozygotes) were tested at midline forehead by using a linear large-band probe with a frequency ranging from 6 to 15 MHz to determine epidermal thickness. Variance and linear regression analyses were performed. Regression coefficients were then used to obtain measurements of thickness corrected for age and sex. RESULTS: GJB2 obligate carriers had a significant increase in epidermal thickness compared with control subjects. GJB2 status explains about 50.0% of this variability, whereas an additional 25.0% is explained by sex and age. Results led to the development of a possible screening protocol with a 98.0% sensitivity and 92.8% specificity in subjects aged 2080 years, with a likelihood ratio of a positive test of 14:1. Even better results (100% sensitivity and 98.9% specificity) were obtained in an analysis of people of only reproductive age. CONCLUSION: Epidermal thickening in the white population owing to GJB2 carrier status can be detected by using US. This measurement could provide a simple, noninvasive, rapid, and sensitive test for carrier screening.


Asunto(s)
Conexinas/genética , Epidermis/diagnóstico por imagen , Pruebas Genéticas/métodos , Pérdida Auditiva/epidemiología , Pérdida Auditiva/genética , Medición de Riesgo/métodos , Ultrasonografía/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Conexina 26 , Femenino , Predisposición Genética a la Enfermedad/genética , Heterocigoto , Humanos , Incidencia , Italia/epidemiología , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y Especificidad , Adulto Joven
10.
Mol Genet Genomic Med ; 7(3): e546, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30628197

RESUMEN

In this paper, is reported the identification of two chimeric patients, a rare finding if sexual abnormalities are absent. However, their chimeric condition is responsible at least for the Silver-Russell phenotype observed in one of the two patients. By single nucleotide polymorphism-array analyses, it was possible to clearly define the mechanism responsible for this unusual finding, underlining the importance of this technique in bringing out the perhaps submerged world of chimeras.


Asunto(s)
Quimerismo , Pruebas Genéticas/métodos , Polimorfismo de Nucleótido Simple , Síndrome de Prader-Willi/genética , Síndrome de Silver-Russell/genética , Niño , Femenino , Humanos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Síndrome de Prader-Willi/patología , Síndrome de Silver-Russell/patología
11.
Eur J Hum Genet ; 26(1): 85-93, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29184170

RESUMEN

Syndromes caused by copy number variations are described as reciprocal when they result from deletions or duplications of the same chromosomal region. When comparing the phenotypes of these syndromes, various clinical features could be described as reversed, probably due to the opposite effect of these imbalances on the expression of genes located at this locus. The NFIX gene codes for a transcription factor implicated in neurogenesis and chondrocyte differentiation. Microdeletions and loss of function variants of NFIX are responsible for Sotos syndrome-2 (also described as Malan syndrome), a syndromic form of intellectual disability associated with overgrowth and macrocephaly. Here, we report a cohort of nine patients harboring microduplications encompassing NFIX. These patients exhibit variable intellectual disability, short stature and small head circumference, which can be described as a reversed Sotos syndrome-2 phenotype. Strikingly, such a reversed phenotype has already been described in patients harboring microduplications encompassing NSD1, the gene whose deletions and loss-of-function variants are responsible for classical Sotos syndrome. Even though the type/contre-type concept has been criticized, this model seems to give a plausible explanation for the pathogenicity of 19p13 microduplications, and the common phenotype observed in our cohort.


Asunto(s)
Anomalías Múltiples/genética , Duplicación Cromosómica , Cromosomas Humanos Par 19/genética , Discapacidad Intelectual/genética , Factores de Transcripción NFI/genética , Anomalías Múltiples/patología , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Discapacidad Intelectual/patología , Masculino , Síndrome
12.
Gene ; 565(1): 146-9, 2015 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-25839933

RESUMEN

Neurodevelopmental disorders are a group of diseases characterized by either structural or functional alterations. The clinical spectrum can vary from isolated intellectual disability to more complex syndromes. Molecular karyotyping can explain 14%-18% of cases due to the presence of large pathogenic CNVs. Moreover, small CNVs involving single genes might result in a monogenic disease. In this article we report two cases of intragenic CTNND2 deletion, detected by molecular karyotyping, in patients with isolated intellectual disability.


Asunto(s)
Cateninas/genética , Discapacidad Intelectual/genética , Cromosomas Humanos Par 5/genética , Eliminación de Gen , Humanos , Discapacidad Intelectual/patología , Cariotipificación , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Catenina delta
13.
J Crohns Colitis ; 8(8): 770-4, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24486179

RESUMEN

Transforming growth factor beta is a pleiotropic cytokine which plays a central role in the homeostasis of the immune system. A complex dysregulation of its signaling occurs in Loeys-Dietz syndrome, a monogenic disorder caused by mutations of transforming growth factor beta receptors type 1 or type 2, characterized by skeletal involvement, craniofacial abnormalities, and arterial tortuosity with a strong predisposition for aneurysm and dissection. In addition, several immunologic abnormalities have been described in these patients, including an increased risk of allergic disorders as well as eosinophilic gastrointestinal disorders. The occurrence of inflammatory bowel disorders has been also reported, but it is poorly documented. We describe two unrelated children with Loeys-Dietz syndrome affected by severe chronic inflammatory colitis appearing at an early age. The intestinal disease presented similar features in both patients, including a histopathological picture of non-eosinophilic chronic ulcerative colitis, striking elevation of inflammatory markers, and a distinctly severe clinical course leading to failure to thrive, with resistance to multiple immunosuppressive treatments. One of the patients also presented autoimmune thyroiditis. Our report confirms that chronic ulcerative colitis may be associated with Loeys-Dietz syndrome. This finding suggests that an alteration of transforming growth factor beta signaling may by itself predispose to inflammatory colitis in humans, and represent an invaluable model to understand inflammatory bowel diseases.


Asunto(s)
Enfermedades Inflamatorias del Intestino/fisiopatología , Transducción de Señal/fisiología , Factor de Crecimiento Transformador beta/fisiología , Preescolar , Colon/patología , Colonoscopía , Femenino , Humanos , Lactante , Enfermedades Inflamatorias del Intestino/congénito , Enfermedades Inflamatorias del Intestino/patología , Síndrome de Loeys-Dietz/patología , Síndrome de Loeys-Dietz/fisiopatología , Masculino
14.
Gene ; 492(1): 315-8, 2012 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-22062632

RESUMEN

Deletions of the short arm of chromosome 2 are exceedingly rare, having been reported in few patients. Furthermore most cases with deletion in 2p11.2-p12 have been studied using standard karyotype and so it is not possible to delineate the precise size of deletions. Here, we describe a 9-year-old girl with a 9.4 Mb de novo interstitial deletion of region 2p11.2-p12 identified by SNP array analysis. The deleted region encompasses over 40 known genes, including LRRTM1, CTNNA2 and REEP1, haploinsufficiency of which could explain some clinical features of this patient such as mental retardation, speech delay and gait abnormalities. A comparison of our case with previously reported patients who present deletions in 2p11.2-p12 was carried out. Our case adds new information to the deletion of 2p11.2-p12, improving the knowledge on this rearrangement.


Asunto(s)
Anomalías Múltiples/genética , Cromosomas Humanos Par 2 , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Polimorfismo de Nucleótido Simple , Eliminación de Secuencia , Niño , Femenino , Humanos , Discapacidad Intelectual/genética
15.
PLoS One ; 7(8): e43799, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22952768

RESUMEN

Usher syndrome (USH) is a clinically and genetically heterogeneous disorder characterized by visual and hearing impairments. Clinically, it is subdivided into three subclasses with nine genes identified so far. In the present study, we investigated whether the currently available Next Generation Sequencing (NGS) technologies are already suitable for molecular diagnostics of USH. We analyzed a total of 12 patients, most of which were negative for previously described mutations in known USH genes upon primer extension-based microarray genotyping. We enriched the NGS template either by whole exome capture or by Long-PCR of the known USH genes. The main NGS sequencing platforms were used: SOLiD for whole exome sequencing, Illumina (Genome Analyzer II) and Roche 454 (GS FLX) for the Long-PCR sequencing. Long-PCR targeting was more efficient with up to 94% of USH gene regions displaying an overall coverage higher than 25×, whereas whole exome sequencing yielded a similar coverage for only 50% of those regions. Overall this integrated analysis led to the identification of 11 novel sequence variations in USH genes (2 homozygous and 9 heterozygous) out of 18 detected. However, at least two cases were not genetically solved. Our result highlights the current limitations in the diagnostic use of NGS for USH patients. The limit for whole exome sequencing is linked to the need of a strong coverage and to the correct interpretation of sequence variations with a non obvious, pathogenic role, whereas the targeted approach suffers from the high genetic heterogeneity of USH that may be also caused by the presence of additional causative genes yet to be identified.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Técnicas de Diagnóstico Molecular/métodos , Análisis de Secuencia de ADN/métodos , Síndromes de Usher/diagnóstico , Síndromes de Usher/genética , Preescolar , Exoma/genética , Genoma Humano/genética , Humanos , Proyectos Piloto
16.
J Med Case Rep ; 5: 222, 2011 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-21689463

RESUMEN

INTRODUCTION: Opitz trigonocephaly C syndrome (OTCS) is a rare malformation syndrome with the following features: synostosis of metopic suture, craniofacial abnormalities, severe mental retardation and a multitude of pathological findings affecting almost every organ system. OTCS is associated with a high mortality rate. CASE PRESENTATION: We describe the case of a Caucasian male baby who died at five months of age during surgical correction of the craniofacial anomaly. CONCLUSION: As previously reported, OTCS may have an increased mortality rate during craniofacial surgery. Careful evaluation of surgery risk-benefit ratio is warranted in such patients.

17.
Ophthalmic Genet ; 31(2): 98-100, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20450314

RESUMEN

PURPOSE: Lymphedema-Distichiasis (LD, OMIM 153400) is an autosomal dominant disorder with variable expression. The mutated gene implicated is FOXC2, which encodes for a forkhead transcription factor involved in the development of the lymphatic and vascular system. LD is characterized by late childhood or pubertal onset lymphedema of the limbs and distichiasis. Other associations have been reported, including congenital heart disease, ptosis, scoliosis. CONCLUSIONS: Here we describe a case of LD carrying a de novo frameshift mutation of FOXC2 who presented a prepubertal onset of lower limbs lymphedema and mild distichiasis associated with other anomalies such as webbing neck and ptosis.


Asunto(s)
Anomalías del Ojo/genética , Pestañas/anomalías , Factores de Transcripción Forkhead/genética , Mutación del Sistema de Lectura , Linfedema/genética , Anomalías Múltiples/genética , Adolescente , Cara/anomalías , Humanos , Masculino , Síndrome
18.
Eur J Med Genet ; 53(5): 322-4, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20673819

RESUMEN

Noonan syndrome (NS) is an autosomal dominant, inherited disorder characterized by facial dysmorphism, congenital heart defects, and reduced postnatal growth. Dysregulated RAS-MAPK signalling is the common molecular basis for NS, a genetically heterogeneous disease. Germline mutations in genes encoding small GTPases of the RAS family (KRAS and NRAS), modulators of RAS function (PTPN11, SOS1 and SHOC2) or downstream signal transducers (RAF1) are causative for NS. SOS1 is the second major gene for NS after PTPN11. Compared to patients with mutations in other genes, SOS1 mutation-positive individuals in general tend to have a more favorable outcome, with less short stature and cognitive impairment. We describe two unrelated patients with NS carrying the same heterozygous SOS1 missense mutation (c.1867T > A/p.F623I). The phenotype of both patients is remarkable as they show uncommon clinical features such as pulmonary lymphangiectasis, congenital pleural effusions, severe feeding problems, and laryngomalacia. These findings may be related to the specific mutation present in our two patients, or be part of the SOS1 phenotype. Detailed clinical assessment of large cohorts of patients with NS and SOS1 mutation is required to clarify this initial observation.


Asunto(s)
Mutación de Línea Germinal , Síndrome de Noonan/genética , Proteína SOS1/genética , Preescolar , Genes ras , Heterocigoto , Humanos , Lactante , Recién Nacido , Masculino , Mutación Missense , Fenotipo
19.
Ophthalmic Genet ; 30(2): 103-5, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19373683

RESUMEN

The 4q deletion syndrome shows varying phenotype, ranging from severe and complex malformations, unconformable with life, to more specific findings, as genitourinary, gastrointestinal and cardiac malformations, cleft palate,microcephaly, hypertelorism and abnormal ears and limbs. Strabismus, nystagmus, ophthalmoplegia, and optic nerve anomalies have been rarely described in literature. We report an original case of simultaneous deletion and duplication of chromosome 4q, confirmed by SNPs-array analysis of DNA, and characterized by a previously unreported association between optic nerve hypoplasia and progressive external ophthalmoplegia.


Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 4/genética , Anomalías Craneofaciales/genética , Duplicación de Gen , Oftalmoplejía Externa Progresiva Crónica/genética , Nervio Óptico/anomalías , Niño , Anomalías Craneofaciales/diagnóstico , Humanos , Masculino , Oftalmoplejía Externa Progresiva Crónica/diagnóstico , Polimorfismo de Nucleótido Simple
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA