Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myasthenia gravis (MG) is characterized by muscle weakness due to autoimmunity against the nicotinic acetylcholine receptor (nAChR). MG is associated with polymorphisms in HLA-DQ genes and the aim of the present study was to characterize structural differences in the peptide binding groove of HLA-DQ molecules positively and negatively associated with MG. Three dimensional models of the positively associated DQ2 (DQB1*02) and negatively associated DQ6 (DQB1*0603) molecules were constructed by homology modeling techniques. The differences in peptide binding properties were primarily localized to peptide-anchor pockets P7 and P9, which might be of importance for the binding of disease-associated peptides from the nAChR.
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PMID:Structural differences between HLA-DQ molecules associated with myasthenia gravis characterized by molecular modeling. 962 3

Narcolepsy-Cataplexy (NC) is a neurological disorder associated with the human leukocyte antigen HLA DR2. This is a prerequisite for the disease in 95 to 98% of Caucasian patients. It has been demonstrated that the HLA DQB1*0602 allele is a better marker for narcolepsy than DRB1*1501 (DR2). We present a DR-negative and DQB1*0602-positive Caucasian Spanish patient with a very unusual genotype. A 20-year-old male presented with a 12-year history of excessive daytime sleepiness and sudden muscle weakness caused by laughter and disturbed nocturnal sleep. He had never presented hypnagogic hallucinations or sleep paralysis. The family history was negative. Physical and neurological examinations were normal. The Epworth Sleepiness Scale score was 21/24, The Ullanlinna Scale score was 20/40. The polysomnographic recording showed short sleep latency, increased percentage of stage 1 (St 1), increased number of body movements and decreased sleep efficiency index. MSLT data: mean sleep latency of 1 minute and three sleep onset rapid eye movement (REM) periods (SOREMPs). HLA phenotype: A1, A11; Cw5, Cw7; B44, B39; Bw4, Bw6; DR4, DR8; DR53; DQ6, DQ8 and at the gene level: DRB1*0402, DQB1*0302; DRB1*0806, DQB1*0602. The DRB1*0806 and DQB1*0602 genotype is very infrequent in NC and identical to one African-American case in the series by Mignot et al. (1997a), and to a Caucasian case in another series by Mignot et al. (1997b). This indicates the genetic heterogeneity of the NC.
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PMID:Narcolepsy-cataplexy syndrome associated with DRB1*0806-DQB*0602 haplotype in a Caucasian patient. 1138 79

We report a 24-year-old man with narcolepsy initially suffered from cataplexy and sleep paralysis. From May 2000, at age 23 he experienced two kinds of recurrent episodes of weakness without altered consciousness; one was provoked by emotion and excitement, the other occurred spontaneously on onset of sleep without hallucination. He denied having daytime sleepiness and did not experience hypnagogic hallucinations. In July 2000, at our hospital he received the first medical examinations, of which physical and neurological results were unremarkable. A magnetic resonance imaging scan of the brain also gave unremarkable results. The initial diagnosis was epilepsy, and anti-convulsant drugs were begun in August 2000. The weakness episodes were not lessened by the treatment with carbamazepine, sodium valproate or clonazepam, and he was admitted to our clinic in April 2001 for further examinations. Human leukocyte antigen testing was positive for DR15 (DR2) and DQ6 (DQ1). The routine electroencephalographam detected no epileptic discharge or paradoxical alpha blocking. A polysomnogram showed a sleep onset REM sleep period and sleep fragmentation, but there was no apnea or periodic leg movements. A multiple sleep latency test showed a mean sleep latency of 1.8 min and REM sleep in three of five naps. These findings suggested probable narcolepsy, so we examined the hypocretin-1 (orexin A) concentration in his cerebrospinal fluid (CSF). It was below the detection limit of the assay (< 40 pg/mL). The final diagnosis in April 2001 was narcolepsy. Making an initial diagnosis of incomplete or atypical narcolepsy is difficult for clinicians. A delay in diagnosis, however, may produce personal and social problems for narcoleptic patients. We believe that an examination of CSF hypocretin-1 aids in the early diagnosis of narcolepsy.
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PMID:[Nacrolepsy manifesting initially as cataplexy and sleep paralysis: usefulness of CSF hypocretin-1 examination for early diagnosis]. 1247 94