ABSTRACT
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.
Subject(s)
Choanal Atresia/metabolism , Clubfoot/metabolism , Deafness/congenital , Hand Deformities, Congenital/metabolism , Heart Defects, Congenital/metabolism , Intellectual Disability/metabolism , Mandibulofacial Dysostosis/metabolism , Micrognathism/metabolism , Mutation , Pierre Robin Syndrome/metabolism , Ribs/abnormalities , Spliceosomes/metabolism , Choanal Atresia/genetics , Clubfoot/genetics , DEAD-box RNA Helicases/genetics , Deafness/genetics , Deafness/metabolism , Eukaryotic Initiation Factor-4A/genetics , Facies , Female , Hand Deformities, Congenital/genetics , Heart Defects, Congenital/genetics , Humans , Intellectual Disability/genetics , Male , Mandibulofacial Dysostosis/genetics , Micrognathism/genetics , Peptide Elongation Factors/genetics , Pierre Robin Syndrome/genetics , RNA Splicing Factors , RNA-Binding Proteins/genetics , Ribonucleoprotein, U5 Small Nuclear/genetics , Ribs/metabolism , Spliceosomes/geneticsABSTRACT
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.
Subject(s)
Craniofacial Abnormalities , Abnormalities, Multiple/genetics , Child , Craniofacial Abnormalities/genetics , Facies , Female , Fetal Growth Retardation/genetics , Fingers/abnormalities , Genes, Recessive , Humans , SyndromeABSTRACT
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.
Subject(s)
Abnormalities, Multiple/pathology , Brain/abnormalities , Brain/diagnostic imaging , Cleft Lip/pathology , Cleft Palate/pathology , Developmental Disabilities/pathology , Ear/abnormalities , Face/abnormalities , Heart Defects, Congenital/pathology , Humans , Infant, Newborn , Male , Syndactyly/pathology , Syndrome , Tomography, X-Ray ComputedABSTRACT
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.
Subject(s)
Abnormalities, Multiple/pathology , Abnormalities, Multiple/genetics , Adult , Brazil , Child, Preschool , Cleft Palate/pathology , Ear, External/abnormalities , Female , Finger Joint/abnormalities , Follow-Up Studies , Foot Deformities, Congenital/pathology , Growth Disorders/congenital , Humans , Infant , Intellectual Disability/pathology , Male , Microcephaly/pathology , Middle Aged , SyndromeABSTRACT
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.
