Microdeletions including FMR1 in three female patients with intellectual disability - further delineation of the phenotype and expression studies.

Fragile X syndrome (FXS) is one of the most common causes of intellectual disability/developmental delay (ID/DD), especially in males. It is caused most often by CGG trinucleotide repeat expansions, and less frequently by point mutations and partial or full deletions of the FMR1 gene. The wide clinical spectrum of affected females partly depends on their X-inactivation status. Only few female ID/DD patients with microdeletions including FMR1 have been reported. We describe 3 female patients with 3.5-, 4.2- and 9.2-Mb de novo microdeletions in Xq27.3-q28 containing FMR1. X-inactivation was random in all patients, yet they presented with ID/DD as well as speech delay, macrocephaly and other features attributable to FXS. No signs of autism were present. Here, we further delineate the clinical spectrum of female patients with microdeletions. FMR1 expression studies gave no evidence for an absolute threshold below which signs of FXS present. Since FMR1 expression is known to be highly variable between unrelated females, and since FMR1 mRNA levels have been suggested to be more similar among family members, we further explored the possibility of an intrafamilial effect. Interestingly, FMR1 mRNA levels in all 3 patients were significantly lower than in their respective mothers, which was shown to be specific for patients with microdeletions containing FMR1.

Mutations in FAM20C are associated with lethal osteosclerotic bone dysplasia (Raine syndrome), highlighting a crucial molecule in bone development.

The generation and homeostasis of bone tissue throughout development and maturity is controlled by the carefully balanced processes of bone formation and resorption. Disruption of this balance can give rise to a broad range of skeletal pathologies. Lethal osteosclerotic bone dysplasia (or, Raine syndrome) is an autosomal recessive disorder characterized by generalized osteosclerosis with periosteal bone formation and a distinctive facial phenotype. Affected individuals survive only days or weeks. We have identified and defined a chromosome 7 uniparental isodisomy and a 7p telomeric microdeletion in an affected subject. The extent of the deleted region at the 7p telomere was established by genotyping microsatellite markers across the telomeric region. The region is delimited by marker D7S2563 and contains five transcriptional units. Sequence analysis of FAM20C, located within the deleted region, in six additional affected subjects revealed four homozygous mutations and two compound heterozygotes. The identified mutations include four nonsynonymous base changes, all affecting evolutionarily conserved residues, and four splice-site changes that are predicted to have a detrimental effect on splicing. FAM20C is a member of the FAM20 family of secreted proteins, and its mouse orthologue (DMP4) has demonstrated calcium-binding properties; we also show by in situ hybridization its expression profile in mineralizing tissues during development. This study defines the causative role of FAM20C in this lethal osteosclerotic disorder and its crucial role in normal bone development.

Comparing treatment intensities of tactile-thermal application.

The purpose of this study was to investigate the relationships of four intensities of tactile-thermal application (TTA) to changes in duration of stage transition (DST) and performance on a newly designed scale of penetration and aspiration by groups of patients made dysphagic by stroke. Patients were randomly assigned to receive 150, 300, 450, or 600 trials of TTA during each of 2 weeks. Data on the time required to provide such treatment, the actual number of trials clinicians were able to provide, and on the influence of the four intensities are provided. No single intensity emerged as the most therapeutic. It is suggested that subsequent studies with larger groups include intensities between 300 and 550.

Temperature acceleration in cold oral stimulation.

This study measured the temperature acceleration of a cold probe as it contacts human tissue. Both the effects of touching a cold probe to the oral cavity were investigated. The results indicated a rapid warming pattern. This warming is effected first by temperature changes resulting from the probe being moved from ice into room temperature and second by the contact to oral mucosa. In fact, in some cases, the probe had reached minimal cold sensation levels by the time it reached the oral cavity. Results also indicated that 6 sec after the probe is lifted from the ice, the temperature closely approximates temperatures perceived as warm or at least neutral, but not cold.

Auditory event-related potential probes and behavioral measures of aphasia.

This study examined the relationship between an auditory event-related potential probe technique measure of differential hemispheric processing and traditional tests of aphasia in aphasic patients. Subjects were 10 aphasic and 10 normal adult males. The results of the electrophysiological measures indicated that the aphasic subjects responded differently from the normal group particularly when the task required processing of verbal information. During the verbal task the aphasic group showed higher amplitude right hemisphere responses as compared to left. The normal group showed little hemispheric task related asymmetries. The pattern of electrical asymmetry in the aphasic group seems to be an indicator of severity as measured by traditional aphasia examinations.

Cueing verbs: a treatment strategy for aphasic adults (CVT).

This investigation demonstrated that the treatment protocol, "Cueing Verbs: A Treatment Strategy for Aphasic Adults" (hereafter referred to as CVT), was an effective rehabilitation technique. Specifically, this CVT was shown to be beneficial with marked/moderate to mild fluent aphasic adults. Additionally, the study addressed such issues as optimal treatment frequencies, treatment initiation and termination points, and criteria for success and failure. Finally, the six-tier hierarchy of treatment levels are presented with all variables operationally defined.

Speech and language findings in a chronic hemodialysis patient: a case report.

The speech and language findings in one patient who underwent chronic hemodialysis therapy are presented. The patient's degenerating physical status was first signaled by stutteringlike repetitions. The speech diagnosis is mixed dysarthria, apraxia of speech, and aphasia. Clinical implications are discussed.