Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aside from social deficits, Asperger and autistic individuals also exhibit motor control abnormalities such as impaired gait, balance, manual dexterity and grip. One brain area that has consistently been reported on autopsy and imaging studies to be abnormal in such individuals is the cerebellum. As the cerebellum controls sensorimotor coordination and lesions here typically cause hypotonia, dysmetria and dyscoordination, we performed a series of quantitative tests aimed at investigating cerebellar function in Asperger individuals. Tests examining visually guided movement (rapid pointing), speeded complex movement (finger tapping, rapid hand turning), muscle tone (catching dropped weight), prediction, coordination and timing (balance, grip force and interval timing) were conducted on 12 Asperger subjects and 12 age and IQ matched controls. In comparison to control subjects, Asperger subject's demonstrated: (i) decreased pointing accuracy and rate, (ii) increased postural instability, and (iii) decreased timing accuracy. IQ was found to co-vary with some parameters of each of these tasks and no further impairments were found on the remaining tests. We suggest that these specific deficits reflect impairment in the ability to integrate sensory input with appropriate motor commands and are consistent with cerebellar dysfunction in Asperger syndrome.
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PMID:Behavioural aspects of cerebellar function in adults with Asperger syndrome. 1632 84

Deletions of the SHOX gene are well documented and cause disproportionate short stature and variable skeletal abnormalities. In contrast interstitial SHOX duplications limited to PAR1 appear to be very rare and the clinical significance of the only case report in the literature is unclear. Mapping of this duplication has now shown that it includes the entire SHOX gene but little flanking sequence and so will not encompass any of the long-range enhancers required for SHOX transcription. We now describe the clinical and molecular characterization of three additional cases. The duplications all included the SHOX coding sequence but varied in the amount of flanking sequence involved. The probands were ascertained for a variety of reasons: hypotonia and features of Asperger syndrome, Leri-Weill dyschondrosteosis (LWD), and a family history of cleft palate. However, the presence of a duplication did not correlate with any of these features or with evidence of skeletal abnormality. Remarkably, the proband with LWD had inherited both a SHOX deletion and a duplication. The effect of the duplications on stature was variable: height appeared to be elevated in some carriers, particularly in those with the largest duplications, but was still within the normal range. SHOX duplications are likely to be under ascertained and more cases need to be identified and characterized in detail in order to accurately determine their phenotypic consequences.
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PMID:Clinical and molecular characterization of duplications encompassing the human SHOX gene reveal a variable effect on stature. 1993 87

We report four new patients with a submicroscopic deletion in 15q24 manifesting developmental delay, short stature, hypotonia, digital abnormalities, joint laxity, genital abnormalities, and characteristic facial features. These clinical features are shared with six recently reported patients with a 15q24 microdeletion, supporting the notion that this is a recognizable syndrome. We describe a case of an ~2.6 Mb microduplication involving a portion of the minimal deletion critical region in a 15-year-old male with short stature, mild mental retardation, attention deficit hyperactivity disorder, Asperger syndrome, decreased joint mobility, digital abnormalities, and characteristic facial features. Some of these features are shared with a recently reported case with a 15q24 microduplication involving the minimal deletion critical region. We also report two siblings and their mother with duplication adjacent and distal to this region exhibiting mild developmental delay, hypotonia, tapering fingers, characteristic facial features, and prominent ears. The deletion and duplication breakpoints were mapped by array comparative genomic hybridization and the genomic structure in 15q24 was analyzed further. Surprisingly, in addition to the previously recognized three low-copy repeat clusters (BP1, BP2, and BP3), we identified two other paralogous low-copy repeat clusters that likely mediated the formation of alternative sized 15q24 genomic rearrangements via non-allelic homologous recombination.
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PMID:Redefined genomic architecture in 15q24 directed by patient deletion/duplication breakpoint mapping. 1955 38