ABSTRACT
[This corrects the article DOI: 10.1155/2020/7353452.].
ABSTRACT
[This corrects the article DOI: 10.1155/2020/7353452.].
ABSTRACT
PURPOSE: Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts. METHODS: We performed exome, targeted capture, and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers. Phenotypic and mutational comparisons were facilitated through data exchange platforms. Whole-transcriptome sequencing was performed on RNA from patient- and control-derived fibroblasts. RESULTS: We identified heterozygous missense variants in TRAF7 as the cause of a developmental delay-malformation syndrome in 45 patients. Major features include a recognizable facial gestalt (characterized in particular by blepharophimosis), short neck, pectus carinatum, digital deviations, and patent ductus arteriosus. Almost all variants occur in the WD40 repeats and most are recurrent. Several differentially expressed genes were identified in patient fibroblasts. CONCLUSION: We provide the first large-scale analysis of the clinical and mutational spectrum associated with the TRAF7 developmental syndrome, and we shed light on its molecular etiology through transcriptome studies.
Subject(s)
Intellectual Disability , Transcriptome , Exome , Germ Cells , Humans , Intellectual Disability/genetics , Mutation, Missense , Phenotype , Transcriptome/genetics , Tumor Necrosis Factor Receptor-Associated Peptides and ProteinsABSTRACT
Shprintzen-Goldberg craniosynostosis syndrome (SGS) is a rare autosomal dominant condition that was first documented in literature in 1982. The disorder is caused by pathogenic variants in the proto-oncogene SKI gene, a known suppressor of TGF-ß activity, located on chromosome 1p36. There is considerable phenotypic overlap with Marfan and Loeys-Dietz syndromes. Common clinical features of SGS include craniosynostosis, marfanoid habitus, hypotonia, dysmorphic facies, cardiovascular anomalies, and other skeletal and connective tissue abnormalities. Ocular manifestations may include hypertelorism, downslanting palpebral fissures, proptosis, myopia, and ectopia lentis. We describe a 25-year-old male with the syndrome. Genetic analysis revealed a novel c.350G>A (p.Arg117His) de novo variant, which was predicted to be pathogenic by the CTGT laboratory. The patient presented with dysmorphic features, marfanoid habitus, severe joint contractures, mitral valve insufficiency, aortic root dilatation, and a history of seizures. His ocular manifestations included hypertelorism, downslanting palpebral fissures, bilateral ptosis, and high myopia. Ophthalmic manifestations are an integral component of the syndrome; however, they have not been well characterized in the literature. From a systematic review of previously published cases to date, we summarize the eye and ocular adnexa manifestations reported.
ABSTRACT
Reported speech, wherein one quotes or paraphrases the speech of another, has been studied extensively as a set of linguistic and discourse practices. Researchers agree that reported speech is pervasive, found across languages, and used in diverse contexts. However, to date, there have been no studies of the use of reported speech among individuals with aphasia. Grounded in an interactional sociolinguistic perspective, the study presented here documents and analyzes the use of reported speech by 7 adults with mild to moderately severe aphasia and their routine communication partners. Each of the 7 pairs was videotaped in 4 everyday activities at home or around the community, yielding over 27 hr of conversational interaction for analysis. A coding scheme was developed that identified 5 types of explicitly marked reported speech: direct, indirect, projected, indexed, and undecided. Analysis of the data documented reported speech as a common discourse practice used successfully by the individuals with aphasia and their communication partners. All participants produced reported speech at least once, and across all observations the target pairs produced 400 reported speech episodes (RSEs), 149 by individuals with aphasia and 251 by their communication partners. For all participants, direct and indirect forms were the most prevalent (70% of RSEs). Situated discourse analysis of specific episodes of reported speech used by 3 of the pairs provides detailed portraits of the diverse interactional, referential, social, and discourse functions of reported speech and explores ways that the pairs used reported speech to successfully frame talk despite their ongoing management of aphasia.
