Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rare case of facioscapulohumeral muscular dystrophy with an early onset and progression is described. The patient had mental retardation, sensorineural hearing loss, and marked tortuosity of the retinal arterioles. On reviewing previous reports of related cases, our case and those of Small shared similar clinical manifestations, although the retinal findings in our patient were different from the typical Coats' disease of Small's patients. However, we postulate that these cases represent a specific nosological entity, although genetic transmission has yet to be proven.
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PMID:Facioscapulohumeral dystrophy associated with mental retardation, hearing loss, and tortuosity of retinal arterioles. 359 27

We report a 31-year-old man with facioscapulohumeral muscular dystrophy who had congenital anomalies and mental retardation. Southern blot analysis, using the probe p13E-11, displayed an abnormal EcoRI DNA fragment that reflect DNA rearrangements in facioscapulohumeral muscular dystrophy. In addition, high-resolution cytogenetic study revealed an interstitial deletion of the short arm chromosome 9: 46,XY,del(9)(p.22.1p24.1).
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PMID:Facioscapulohumeral muscular dystrophy with chromosome 9p deletion. 861 37

The gene for facioscapulohumeral muscular dystrophy (FSHD) has been mapped to chromosome 4q35. In most patients with FSHD, a deletion of 3.3 kb tandemly repeated units within the EcoRI fragment that can be detected by probe p13E-11 is associated with the disease. To elucidate the relation between the phenotype and the genotype in FSHD, we examined 91 Japanese unrelated families with a clinical diagnosis of FSHD (140 patients, 205 healthy individuals). Of these, 78 families (86%) had 4q35-FSHD (127 patients), in which 20 patients (20/127, 16%) were classified as early onset FSHD. We found that all nine patients with the smallest EcoRI fragments (10 to 11 kb) were classified among the early onset group (9/20, 45%), and these patients showed a high frequency of both epilepsy (4/9, 44%) and mental retardation (8/9, 89%). In contrast, none of the remaining patients with 4q35-FSHD had epilepsy or mental retardation. We conclude that FSHD patients with a large gene deletion in the FSHD gene region tend to have a higher chance of showing severe clinical phenotypes with CNS abnormalities. This finding may have practical implications for genetic counseling, although the molecular genetic background remains unclear.
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PMID:Epilepsy and mental retardation in a subset of early onset 4q35-facioscapulohumeral muscular dystrophy. 963 29

Two cases of early onset facioscapulohumeral muscular dystrophy (FSHD) with mental retardation and epilepsy are reported. They were sporadic, unrelated, severely affected females. In both cases, Southern blot analysis of the EcoRI-digested genomic DNA, using probes p13E-11 and pFR-1, detected the shortest 10 kb EcoRI fragments reported to date. Patient 1 showed infantile spasms at the age of 4 months and localization-related epilepsy at the age of 2.5 years. Muscular atrophy in the face, shoulder girdle and upper arms was observed from the age of 4 years. In Patient 2, lack of facial expression was noticed since the age of 1 year, and at 4 years she was noted to have a loss of bilateral upward gaze. She developed localization-related epilepsy at the age of 9 years. From the age of 10 years, weakness of the lower limbs progressed and she became wheelchair-bound at the age of 14 years and 8 months. She had moderate sensorineural hearing loss, a loss of bilateral upward gaze and tongue atrophy. Their IQs were 33 and 45, respectively. The two patients suggest that mental retardation and epilepsy may be part of the clinical spectrum of FSHD, especially in very early onset patients with large deletions.
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PMID:Two cases of chromosome 4q35-linked early onset facioscapulohumeral muscular dystrophy with mental retardation and epilepsy. 981 May 58

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant form of muscular dystrophy characterized by progressive weakness and wasting of the facial, shoulder-girdle and upper arm muscles. The gene locus for FSHD is mapped to the subtelomeric region of chromosome 4q35, in which smaller EcoRI fragments (10 to 33 kb) are detected in most families by Southern blot analysis. The purpose of this study is to clarify the frequency and clinical/genetical features of early-onset FSHD in Japanese patients with 4q35-FSHD. In a series of 231 patients from 145 families with 4q35-FSHD, there were 31 patients (13.4%; male: female = 12:19) of 29 families (20%) with early-onset FSHD, 16 of whom were sporadic. Genetic analysis revealed that they had significantly smaller sized EcoRI fragments (range, 10 to 23 kb; mean 14.1 kb) than the other patients (range, 12 to 33 kb; mean 19.6 kb) (p < 0.001, U-test). All patients with the smallest EcoRI fragments (10 to 11 kb) were sporadic cases with early onset. Mental retardation (10/11) and epilepsy (4/11) was often observed in them, but not in the other patients. In early-onset FSHD, tongue muscle involvement (8/31) and swallowing disturbance (2/31), which has been regarded as exclusion criteria of FSHD, were also present. The onset of gait disturbance was significantly earlier (mean age = 11.9) in early-onset FSHD compared to the other group (mean age = 28.7). All patients with early-onset FSHD showed gait disturbance before 28 years of age. In conclusion, Japanese early-onset FSHD patients tend to have large gene deletions on chromosome 4q35, and show severe and variable phenotypes.
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PMID:[Clinical and genetical features of Japanese early-onset facioscapulohumeral muscular dystrophy]. 1213 83

Previous studies found that some patients with severe, early onset facioscapulohumeral muscular dystrophy (FSHD) present epilepsy and mental retardation. This suggests a functional involvement of central nervous system in severe FSHD. It is unknown whether minor functional changes of central nervous system are also present in less severe forms of FSHD. To investigate this, we examined the excitability of neuronal networks of the motor cortex with a range of transcranial magnetic stimulation paradigms in 20 FSHD patients with heterogeneous clinical severity and compared the data with that from 20 age-matched healthy individuals and from 6 age-matched patients with other muscle diseases. There was significantly less intracortical inhibition in FSHD patients (mean responses +/- SD reduced to 58.1+/-43.5% of the test size) than in controls (mean responses +/- SD reduced to 29.3+/-13.5% of the test size; P=0.025) and in patients with other muscle diseases (mean responses +/-SD, reduced to 30.6+/-11.7% of the test size; P=0.046). No significant difference was found between the control group and patients with other muscle diseases (P=0.970).
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PMID:Changes in motor cortex excitability in facioscapulohumeral muscular dystrophy. 1465 11

Facioscapulohumeral muscular dystrophy (FSHD), a pathology primarily characterized by involvement of the muscles in the face, shoulder and upper arm, can be associated to several CNS disorders, including sensorineural hearing deficits, schizophrenia, epilepsy and mental retardation. Aim of our study was to verify if brain tissue volumes, as measured by segmentation of MRI studies, are altered in FSHD. Volumes of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were compared, taking into account head size age and sex, both globally (by multiple regression analysis) and regionally (by optimized voxel-based morphometry-VBM) in thirty patients with FSHD and 39 normal subjects (NS). FSHD patients had significantly lower GM volumes and higher CSF volumes (P < 10(-4)). GM loss showed a borderline correlation with clinical severity (P < 0.05). Brain tissue volumes did not correlate with disease duration, size of the genetic deletion, age at onset and the presence at MRI of WM hyperintensities (detected in 4/22 patients). At VBM three clusters of GM loss were detected, in the left precentral cortex (Brodmann areas 6, 2 and 44, P < 10(-14) corrected for multiple comparisons at cluster level), in the anterior cingulate (Brodmann areas 33, 24 and 11, P < 10(-4)) and in the right fronto-polar region (Brodmann area 10, P < 5.10(-3)). To the best of our knowledge, this is the first study to demonstrate a reduction in GM volume in FSHD. We hypothesize that localized GM loss in FSHD is the consequence of a selective involvement of specific CNS structures.
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PMID:Modifications of brain tissue volumes in facioscapulohumeral dystrophy. 1680 75

Facioscapulohumeral muscular dystrophy is one of the most prevalent muscular dystrophies in the world, resulting from the deletion of tandem repeats on chromosome 4q35. Extramuscular associations include sensorineural hearing loss, mental retardation, and epilepsy. These manifestations are commonly found in those with large deletions and early onset of weakness. A 26-year-old patient with a long-standing history of hearing loss, learning disabilities, and epilepsy presented with new-onset weakness and an elevated serum creatinine kinase level. Genetic testing confirmed sporadic facioscapulohumeral muscular dystrophy with a fragment length of 12 kilobases (normal > 35 kilobases). This unique presentation suggests that facioscapulohumeral muscular dystrophy should be considered in the differential diagnosis of children with cognitive impairment, seizures, and hearing loss.
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PMID:Facioscapulohumeral muscular dystrophy can be a cause of isolated childhood cognitive dysfunction. 1690 30

We report here a case of a 20-year-old woman with facioscapulohumeral muscular dystrophy (FSHD). In this patient, the involvement of facial muscle had been present since early childhood, but obscured due to the complication of profound mental retardation. Epilepsy emerged at eight years of age. Symmetrical limb muscle weakness appeared at 15 years of age, which progressed such that she was wheelchair-bound at 18 years of age. An elevated serum creatine kinase, predominant involvement of hamstrings, scapular and abdominal muscles, as well as an impaired stapedial reflex at high tune, were compatible with the clinical features of FSHD. The diagnosis of 4q35-FSHD was confirmed by detection of a 10kb EcoRI fragment with a p13E-11 probe on a Southern blot. The intellectual disability in this patient was the most severe of all FSHD patients reported to date and has hindered a correct diagnosis. This entity should be included in the differential diagnoses for patients with muscular symptoms and accompanying mental retardation.
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PMID:Facioscapulohumeral muscular dystrophy with severe mental retardation and epilepsy. 1701 May 49

FXR1P is one of two autosomal paralogs of the fragile X mental retardation protein FMRP. The absence of FMRP causes fragile X syndrome, the leading cause of hereditary mental retardation. FXR1P plays an important role in normal muscle development and has been implicated in facioscapulohumeral muscular dystrophy (FSHD). Its absence also causes cardiac abnormalities in both mice and zebrafish. To examine miRNA-mediated regulation of FMRP and FXR1P, we studied their expression in a conditional Dicer knockdown cell line, DT40. We found that FXR1P, but not FMRP, is significantly increased upon Dicer knockdown and the consequent reduction of miRNAs, suggesting that FXR1P is regulated by miRNAs while FMRP is not in DT40 cells. Expression of a luciferase reporter bearing the 3' untranslated region (3'UTR) of FXR1 was significantly increased in the absence of miRNAs, confirming miRNA-mediated regulation of FXR1P, while a luciferase reporter bearing the FMR1 3'UTR was not. We identified one of the regulatory regions in the 3'UTR of FXR1 by removing a conserved, 8-nucleotide miRNA seed sequence common to miRNAs 25, 32, 92, 363, and 367 and demonstrated loss of miRNA-mediated suppression. Treatment with specific miRNA hairpin inhibitors to each of the miRNAs in the seed sequence showed that miRs 92b, 363, and 367 regulated FXR1P expression. Accordingly, overexpression of the miRNA 367 mimic significantly decreased endogenous FXR1P expression in human cell lines HEK-293T and HeLa. We report for the first time that FXR1P is regulated through miRNA binding, with one site being the miR-25/32/92/363/367 seed sequence.
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PMID:Fragile X protein family member FXR1P is regulated by microRNAs. 2051 10


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