Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0848771 (neurological disability)
 928 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary motor and sensory neuropathy (HMSN) is one of the most frequently inherited causes of peripheral neurological disability. To date, the classification has been based on clinical, histological and genetic grounds. Due to increased genetic knowledge at the molecular level in recent years, diagnosis of the different subtypes has been considerably improved and their relationship clarified. We describe three generations of a family with HMSN IA (Charcot-Marie-Tooth disease IA = CMT 1A) with a genetic defect mapped to chromosome 17 and show the importance of genetic testing. Even in benign and clinically non-manifested causes of the disease, an early and non-invasive diagnosis should be made by genetic testing to identify affected persons; thus, nerve biopsy can be abandoned. Operations of pes cavus, which are not indicated and are often complicated by delayed healing, may be avoided. Instead, patients should undergo early physiotherapy and be counselled about their professional careers and family planning.
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PMID:[Charcot-Marie-Tooth syndrome. Clinico-genetic correlation in an affected family]. 885 Dec 97

The proband was a 22-year-old man with a complaint of progressive weakness in his lower limbs. His clinical diagnosis of hereditary motor and sensory neuropathy (HMSN) type 1 was made based on the neurological findings and the results of peripheral nerve conduction studies and of histological studies of the sural nerve obtained on biopsy. The molecular genetic studies revealed arginine-to-histidine substitution at amino acid 98 of the Po protein in the proband. Therefore, the final diagnosis of HMSN type 1B was made. The same mutation was found in his mother and his two sisters. The neurological disability score of the proband was 69. It was 24 for his affected mother. The scores were 16 and 20 for the two affected sisters. The reason why the proband showed the highest score was considered to be the presence of the marked muscle weakness in the lower limbs found only in the proband. Therefore, it was concluded that the neurological disability score differs greatly among the affected members even with the same genetic abnormality in the same generation of the same family with HMSN type 1B. The affected family member with a low neurological disability score may be clinically undiagnosed.
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PMID:[A family of hereditary motor and sensory neuropathy type 1B showing a marked difference of neurological disability score among affected family members]. 1043 62

Inherited peripheral neuropathies (IPN) are one of the most frequent inherited causes of neurological disability characterized by considerable phenotypic and genetic heterogeneity. Based on clinical and electrophysiological properties, they can be subdivided into three main groups: HMSN, dHMN, and HSN. At present, more than 50 IPN genes have been identified. Still, many patients and families with IPN have not yet received a molecular genetic diagnosis because clinical genetic testing usually only covers a subset of IPN genes. Moreover, a considerable proportion of IPN genes has to be identified. Here we present results of WES in 27 IPN patients excluded for mutations in many known IPN genes. Eight of the patients received a definite diagnosis. While six of these patients carried bona fide pathogenic mutations in known IPN genes, two patients had mutations in genes known to be involved in other types of neuromuscular disorders. A further group of eight patients carried sequence variations in IPN genes that could not unequivocally be classified as pathogenic. In addition, combining data of WES and linkage analysis identified SH3BP4, ITPR3, and KLHL13 as novel IPN candidate genes. Moreover, there was evidence that particular mutations in PEX12, a gene known to cause Zellweger syndrome, could also lead to an IPN phenotype. We show that WES is a useful tool for diagnosing IPN and we suggest an expanded phenotypic spectrum of some genes involved in other neuromuscular and neurodegenerative disorders. Nevertheless, interpretation of variants in known and potential novel disease genes has remained challenging.
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PMID:Whole-exome sequencing in patients with inherited neuropathies: outcome and challenges. 2462 8