RESUMEN
The spliceosome is a large ribonucleoprotein complex that removes introns from pre-mRNA transcripts. Mutations in EFTUD2, encoding a component of the major spliceosome, have recently been identified as the cause of mandibulofacial dysostosis, Guion-Almeida type (MFDGA), characterized by mandibulofacial dysostosis, microcephaly, external ear malformations and intellectual disability. Mutations in several other genes involved in spliceosomal function or linked aspects of mRNA processing have also recently been identified in human disorders with specific craniofacial malformations: SF3B4 in Nager syndrome, an acrofacial dysostosis (AFD); SNRPB in cerebrocostomandibular syndrome, characterized by Robin sequence and rib defects; EIF4A3 in the AFD Richieri-Costa-Pereira syndrome, characterized by Robin sequence, median mandibular cleft and limb defects; and TXNL4A in Burn-McKeown syndrome, involving specific craniofacial dysmorphisms. Here, we review phenotypic and molecular aspects of these syndromes. Given the apparent sensitivity of craniofacial development to defects in mRNA processing, it is possible that mutations in other proteins involved in spliceosomal function will emerge in the future as causative for related human disorders.
Asunto(s)
Atresia de las Coanas/metabolismo , Pie Equinovaro/metabolismo , Sordera/congénito , Deformidades Congénitas de la Mano/metabolismo , Cardiopatías Congénitas/metabolismo , Discapacidad Intelectual/metabolismo , Disostosis Mandibulofacial/metabolismo , Micrognatismo/metabolismo , Mutación , Síndrome de Pierre Robin/metabolismo , Costillas/anomalías , Empalmosomas/metabolismo , Atresia de las Coanas/genética , Pie Equinovaro/genética , ARN Helicasas DEAD-box/genética , Sordera/genética , Sordera/metabolismo , Factor 4A Eucariótico de Iniciación/genética , Facies , Femenino , Deformidades Congénitas de la Mano/genética , Cardiopatías Congénitas/genética , Humanos , Discapacidad Intelectual/genética , Masculino , Disostosis Mandibulofacial/genética , Micrognatismo/genética , Factores de Elongación de Péptidos/genética , Síndrome de Pierre Robin/genética , Factores de Empalme de ARN , Proteínas de Unión al ARN/genética , Ribonucleoproteína Nuclear Pequeña U5/genética , Costillas/metabolismo , Empalmosomas/genéticaRESUMEN
We report a Brazilian female patient with a thin and long face, blepharophimosis, minor auricular anomalies, camptodactyly and thoracic and spinal anomalies. The constellation of clinical signs present in this patient is consistent with the diagnosis of Guadalajara camptodactyly syndrome type I. Clinical and genetic aspects concerning this condition are discussed.
Asunto(s)
Anomalías Craneofaciales , Anomalías Múltiples/genética , Niño , Anomalías Craneofaciales/genética , Facies , Femenino , Retardo del Crecimiento Fetal/genética , Dedos/anomalías , Genes Recesivos , Humanos , SíndromeRESUMEN
We report on a male patient with a constellation of malformations, including cleft lip/palate, abnormal ears, ectrodactyly, congenital heart defect (CHD), and growth retardation. A similar association has been previously reported twice [Richieri-Costa and Orquizas (1987) Rev Brasil Genet X:787-792; Giannotti et al. (1995) J Med Genet 32:72-74], and autosomal recessive inheritance was proposed.
Asunto(s)
Anomalías Múltiples/patología , Encéfalo/anomalías , Encéfalo/diagnóstico por imagen , Labio Leporino/patología , Fisura del Paladar/patología , Discapacidades del Desarrollo/patología , Oído/anomalías , Cara/anomalías , Cardiopatías Congénitas/patología , Humanos , Recién Nacido , Masculino , Sindactilia/patología , Síndrome , Tomografía Computarizada por Rayos XRESUMEN
We report on 2 unrelated Brazilian patients, born to non-consanguineous parents, both with multiple anomalies including growth and mental retardation, microcephaly, telecanthus, cleft palate, preauricular skin tags/pit, camptodactyly, and foot anomalies. To our knowledge, this is a previously undescribed formal genesis syndrome. Clinical and genetic aspects are discussed.
Asunto(s)
Anomalías Múltiples/patología , Anomalías Múltiples/genética , Adulto , Brasil , Preescolar , Fisura del Paladar/patología , Oído Externo/anomalías , Femenino , Articulaciones de los Dedos/anomalías , Estudios de Seguimiento , Deformidades Congénitas del Pie/patología , Trastornos del Crecimiento/congénito , Humanos , Lactante , Discapacidad Intelectual/patología , Masculino , Microcefalia/patología , Persona de Mediana Edad , SíndromeRESUMEN
We report on a patient born to normal and nonconsanguineous parents and presenting with strikingly malformed ears, abnormalities of the condyle of the mandible, micrognathia, small mouth, and cleft uvula. The similarity of our patient with those reported previously by Jampol et al. [1998: Am. J. Med. Genet. 75:449-452] led us to suggest that they have the same condition.
