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)

Congenital axonal neuropathy associated with encephalopathy appears to be very rare. Only a few cases have been reported in the literature. In the last 25 years, we have seen seven patients affected by congenital axonal neuropathy with encephalopathy. Biopsies of their sural nerves revealed axonal atrophy and loss of large-diameter nerve fibers. All of these patients presented at birth or soon thereafter with hypotonia associated with distal weakness and diffuse areflexia. Central nervous system manifestations included microcephaly, seizures, and developmental delay. Outcomes were poor. Four children died before age 3 years from respiratory insufficiency or aspiration pneumonia. The three surviving patients manifested severe developmental delay. In our most recent patient, Western-blot analysis of snap-frozen specimens of the temporal and cerebellar cortex demonstrated an absence or marked decrease of microtubule-associated protein types 1A and 2, compared with age-matched control subjects. Calloso-splenial hypogenesis and neurofilament swellings were also documented in the deep white matter and adjacent cortex. The absence or hypo-expression of central nervous system microtubule-associated proteins has never been reported in congenital neuropathies, and may represent a new clinicopathologic entity.
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PMID:Congenital axonal neuropathy and encephalopathy. 1835 5

Mutations of the MAPT (microtubule-associated protein tau) gene are associated with FTLD (frontotemporal lobar degeneration) with tau pathology. These mutations result in a decreased ability of tau to bind MTs (microtubules), an increased production of tau with four MT-binding repeats or enhanced tau aggregation. In two FTLD patients, we recently described CNVs (copy number variations) affecting the MAPT gene, consisting of a partial deletion and a complete duplication of the gene. The partial deletion resulted in a truncated protein lacking the first MT-binding domain, which had a dramatic decrease in the binding to MTs but acquired the ability to bind MAP (microtubule-associated protein) 1-B. In this case, tauopathy probably resulted from both a loss of normal function and a gain of function by which truncated tau would sequester another MAP. In the other FTLD patient, the complete duplication might result in the overexpression of tau, which in the mouse model induces axonopathy and tau aggregates reminiscent of FTLD-tau pathology. Interestingly, the same rearrangement was also described in several children with mental retardation, autism spectrum disorders and dysmorphic features, as well as in a schizophrenic patient. Finally, complete deletions of the MAPT gene have been associated with mental retardation, hypotonia and facial dysmorphism.
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PMID:Copy number variations involving the microtubule-associated protein tau in human diseases. 2281 14