RESUMEN
Camurati-Engelmann disease (CED) [OMIM 131300] is an autosomal dominant sclerosing bone dysplasia recently ascribed to mutations of the transforming growth factor (TGF-beta1) gene on chromosome 19q13.1-q13.3. Five mutations consistently located in the TGF-beta1 propeptide have been hitherto identified in 21 families. Here, we report on TGF-beta1 mutations in one Australian and six European families. Three distinct mutations were identified among seven families: namely, R218H (family 1), R218C (families 2, 6, 7) and C225R (families 3, 4, 5). The three mutations identified in our pedigrees have been previously observed in families of Japanese and Israeli origin and the R218C appears to be the most prevalent mutation worldwide (17/28 reported families). No obvious correlation between the nature of the mutations and the severity of the clinical manifestations could be established, but a marked intrafamilial clinical variability was observed, supporting incomplete penetrance of CED. Interestingly, the polymorphisms in the TGF-beta1 gene showed no correlation with the severity of the disease. We conclude that CED is a clinically variable condition and that this clinical variability is not accounted for by polymorphisms at the TGF-beta1 locus.
Asunto(s)
Síndrome de Camurati-Engelmann/genética , Factor de Crecimiento Transformador beta/genética , Australia , Síndrome de Camurati-Engelmann/diagnóstico por imagen , Cromosomas Humanos Par 19 , Femenino , Francia , Variación Genética , Genotipo , Humanos , Masculino , Fenotipo , Mutación Puntual , Portugal , Radiografía , Factor de Crecimiento Transformador beta1Asunto(s)
Síndrome de Camurati-Engelmann/genética , Cromosomas Humanos Par 19/genética , Heterogeneidad Genética , Mapeo Cromosómico , Femenino , Haplotipos , Humanos , Masculino , Repeticiones de Microsatélite , Linaje , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Portugal/epidemiología , Recombinación GenéticaAsunto(s)
Anticipación Genética , Síndrome de Camurati-Engelmann/genética , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , LinajeRESUMEN
Lenz-Majewski hyperostotic dwarfism is an extremely rare syndrome with moderate to severe mental retardation and no previously identified brain abnormalities. We describe the seventh case and note dysgenesis of the corpus callosum in this patient.
Asunto(s)
Agenesia del Cuerpo Calloso , Enanismo , Hiperostosis , Huesos/diagnóstico por imagen , Preescolar , Cuerpo Calloso/diagnóstico por imagen , Enanismo/diagnóstico por imagen , Femenino , Humanos , Hiperostosis/diagnóstico por imagen , Imagen por Resonancia Magnética , RadiografíaRESUMEN
Immuno-osseous dysplasia is characterised by spondyloepiphyseal dysplasia, lymphopenia with defective cellular immunity, and progressive renal disease. We describe a patient with a severe form of the disease, review the features of another 24 patients, and discuss the previous classification. The differences between the two groups are not striking, and although similarities are greater between affected sibs, the same diagnosis of Schimke immuno-osseous dysplasia should apply to them all. The aetiology and physiopathology of this rare osteochondrodysplasia of presumed autosomal recessive inheritance remain unknown.
Asunto(s)
Huesos/diagnóstico por imagen , Osteocondrodisplasias/diagnóstico por imagen , Huesos/anomalías , Preescolar , Humanos , Enfermedades Renales/complicaciones , Linfopenia/complicaciones , Masculino , Osteocondrodisplasias/clasificación , Osteocondrodisplasias/complicaciones , Pelvis/diagnóstico por imagen , Fenotipo , Radiografía , Columna Vertebral/diagnóstico por imagen , SíndromeRESUMEN
Robinow syndrome was found in two monozygotic twins. We describe the clinical and radiographic manifestations in these patients, both with normal stature and one with omphalocele, with a follow-up of 13 years. Families with Robinow syndrome of both autosomal dominant and recessive inheritance have been reported. We apply the criteria suggested to assign isolated cases to one of the two forms and conclude that autosomal dominant inheritance is more likely.
Asunto(s)
Anomalías Múltiples/patología , Estatura , Enfermedades en Gemelos , Gemelos Monocigóticos , Facies , Humanos , SíndromeRESUMEN
Progressive diaphyseal dysplasia was found in a 3-generation family including 18 affected individuals. We describe the clinical and radiographic manifestations in 6 of 18 patients with this autosomal-dominant bone dysplasia and the good symptomatic response to corticosteroid treatment in one of these. The variability of manifestations of the disease in this family and in others previously described seems to depend on the sex of the patient and the parental origin of the mutation. The patients with more severe symptoms are males who inherited an allele of paternal origin. We suggest that the progressive diaphyseal dysplasia gene has a function in endochondral bone formation and that its mutation is a dynamic one with repeat expansion enhanced in father-to-son transmission.
Asunto(s)
Síndrome de Camurati-Engelmann/genética , Adolescente , Adulto , Síndrome de Camurati-Engelmann/diagnóstico por imagen , Síndrome de Camurati-Engelmann/tratamiento farmacológico , Niño , Femenino , Impresión Genómica , Humanos , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Linaje , Fenotipo , Prednisona/uso terapéutico , Radiografía , Caracteres SexualesRESUMEN
We report the seventh case of the 3C syndrome or Cranio-Cerebello-Cardiac dysplasia. The presence of congenital glaucoma in our patient suggests that this is a previously undescribed feature of this syndrome, which is presumed to be autosomal recessive.
Asunto(s)
Anomalías Múltiples/fisiopatología , Glaucoma/congénito , Encéfalo/anomalías , Femenino , Cardiopatías Congénitas/fisiopatología , Humanos , Recién Nacido , Cráneo/anomalías , SíndromeRESUMEN
We examined the value of the fasting plasma phenylalanine/tyrosine ratio obtained in an ordinary clinical setting for assessing the probability of being a heterozygote for hyperphenylalaninaemia. This biochemical test was found to be of little value in those with a high (66%) prior risk of heterozygosity, because it could not reduce the risk below 12%. However, in a population with a prior risk of only 2%, it discriminates the 3% with a 19% risk from the 97% with a risk of 1.5% or less. This simple method could usefully be applied to such a population, in order to select those at higher risk for further investigation using molecular genetics.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/sangre , Heterocigoto , Fenilalanina/sangre , Tirosina/sangre , Errores Innatos del Metabolismo de los Aminoácidos/genética , Teorema de Bayes , Femenino , Humanos , Masculino , Factores de RiesgoRESUMEN
We review 72 previously reported and 29 new patients with the possible diagnosis of Joubert syndrome. We define diagnostic criteria for this syndrome and present the data available in 94 patients that fulfill our criteria. We present the data regarding the clinical, neuroradiological, and ophthalmological manifestations and the prognosis of these 94 patients. We propose a classification of the patients with this diagnosis in 2 groups: those with retinal dystrophy and those without. Retinal dystrophy runs true in families and was never absent when renal cysts were reported.
Asunto(s)
Anomalías Múltiples/genética , Cerebelo/anomalías , Enfermedades de la Retina/genética , Anomalías Múltiples/diagnóstico , Femenino , Humanos , Masculino , Pronóstico , Enfermedades de la Retina/diagnóstico , Razón de Masculinidad , SíndromeRESUMEN
The Marfan syndrome is an autosomal dominant heritable disorder of connective tissue with prominent involvement of the ocular, skeletal, and cardiovascular systems. The gene on chromosome 15 encoding fibrillin (FBN1), a 350-kDa glycoprotein component of the extracellular microfibril, is the site of defect in most, if not all cases. Complementary DNA sequence reveals a gene composed largely of epidermal growth factor-like repeats, each containing six predictably spaced cysteine residues. To date, two FBN1 gene missense mutations have been reported. Here we describe the identification of three new missense mutations in the FBN1 gene in patients with the Marfan syndrome. All of the 5 characterized missense mutations occur within the epidermal growth factor-like repeats of the FBN1 gene. In addition, 4 of 5 involve the substitution of cysteine residues and 3 of 5 substitute the third cysteine in the epidermal growth factor-like motif consensus sequence. These data suggest that defined residues within EGF-like domains of FBN1 have particular significance and, when altered, play a pivotal role in expression of the Marfan phenotype.