RESUMEN
BACKGROUND: The 10q24 chromosomal region has previously been implicated in split hand foot malformation (SHFM). SHFM3 was mapped to a large interval on chromosome 10q. The corresponding dactylaplasia mouse model was linked to the syntenic locus on chromosome 19. It was shown that the two existing Dac alleles result from MusD-insertions upstream of or within Dactylin (Fbxw4). However, all efforts to find the underlying cause for the human SHFM3 have failed on the analysis of all the genes within the linkage region. Intriguingly a submicroscopic duplication within the critical locus on chromosome 10q24 was associated with the phenotype. METHODS AND RESULTS: As a part of screening for genomic rearrangements in cases with unexplained syndromic limb defects, a cohort of patients was analysed by array comparative genomic hybridisation (CGH). A 10q24 microduplication was detected in two individuals with distal limb deficiencies associated with micrognathia, hearing problems and renal hypoplasia. In addition, in a family with two affected siblings, a somatic/gonadal mosaicism for the microduplication was detected in the apparently healthy mother. Using a high resolution oligoarray further delineation of the duplication size was performed. CONCLUSIONS: The detected 10q24 genomic imbalance in our syndromic patients has a similar size to the duplication in the previously reported individuals with an isolated form of SHFM, thus extending the clinical spectrum of SHFM3. These findings clearly demonstrate the importance of array CGH in the detection of the aetiology of complex, clinically heterogeneous entities.
Asunto(s)
Cromosomas Humanos Par 10 , Proteínas F-Box/genética , Deformidades Congénitas del Pie/genética , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de las Extremidades/genética , Micrognatismo/genética , Mapeo Cromosómico , Cromosomas Artificiales Bacterianos , Estudios de Cohortes , Hibridación Genómica Comparativa , Femenino , Duplicación de Gen , Reordenamiento Génico , Humanos , Hibridación Fluorescente in Situ , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , SíndromeAsunto(s)
Encéfalo/anomalías , Facies , Discapacidad Intelectual/patología , Paraplejía/patología , Adulto , Femenino , HumanosRESUMEN
A girl with mental retardation and multiple minor anomalies was found to have a complex chromosome 9p re-arrangement comprising a deleted, translocated Y chromosome, a deletion of the sex reversal gene region (DMRT1) at 9p, together with an inverted duplication of the more proximal part of 9p. The karyotype was 45,X,der(Y;9)(Ypter-->Yq12::9p21.1-->9p22.2::9p22.2-->9qter) de novo. The karyotypic male, phenotypic female had a dysgerminoma of the left dysplastic ovary. The patient had typical 'trisomy 9p' syndrome, and we propose that the critical region for this phenotype is located between 9p22.1 and 9p22.2.
Asunto(s)
Anomalías Múltiples/genética , Cromosomas Humanos Par 9/genética , Cromosomas Humanos Y/genética , Trastornos del Desarrollo Sexual , Discapacidad Intelectual/patología , Translocación Genética , Anomalías Múltiples/patología , Niño , Bandeo Cromosómico , Femenino , Humanos , Hibridación Fluorescente in Situ , CariotipificaciónRESUMEN
In this paper we report the results of a genetic-diagnostic survey of 116 institutionalized male patients who were moderately to severely retarded. In 31 patients (26.7%) a constitutional cause of their mental impairment was found: chromosomal abnormalities in 11 patients (9.5%), Mendelian disorders in 16 (13.8%), of which 8 fragile X patients (6.9%), and a MCA/MR syndrome in 4 patients (3.4%). Acquired forms of mental retardation occurred in 26 patients (22.4%): CNS-dysfunction due to pre-, peri- or postnatal causes were most likely in 18 patients (15.5%), while infections played a major role in 8 (6.9%). In 59 patients (50.9%) not etiological diagnosis could be made.
Asunto(s)
Aberraciones Cromosómicas/genética , Pruebas Genéticas , Institucionalización , Discapacidad Intelectual/genética , Adulto , Anciano , Anciano de 80 o más Años , Bélgica , Trastornos de los Cromosomas , Síndrome del Maullido del Gato/genética , Diagnóstico Diferencial , Síndrome del Cromosoma X Frágil/genética , Humanos , Masculino , Persona de Mediana Edad , FenotipoRESUMEN
The association of an acoustic neuroma with an ipsilateral venous anomaly or angioma is reported in two patients. In the first, the venous angioma was situated low in the posterior fossa, and was of no significance surgically. In the second, the angioma was strongly attached to the capsule of the tumour. On MRI and angiography the lesion appeared as a large draining vein, encircling the tumour. At operation, extensive dissection of the angioma from the neuroma appeared necessary to prevent venous infarction of the brain stem.