Methods of identifying genetic mutations associated with charcot-marie-tooth neuropathy type 1C

摘要

In one aspect, the invention provides methods of identifying genetic mutations that are associated with peripheral neurological disease. The methods comprise identifying a difference between a nucleic acid sequence of a small integral protein of the lysosome/late endosome (“SIMPLE”) gene from a mammalian subject exhibiting peripheral neuropathy and a nucleic acid sequence of a SIMPLE gene from a subject which is not exhibiting peripheral neuropathy, wherein the difference is a genetic mutation associated with peripheral neurological disease. In another aspect, isolated nucleic acid molecules encoding SIMPLE missense mutations are provided. In another aspect, a method of screening a subject to determine if the subject has a genetic predisposition to develop Charcot-Marie-Tooth type 1C neuropathy is provided. In another aspect, the invention provides kits for determining susceptibility or presence of Charcot-Marie-Tooth type 1C neuropathy in a mammalian subject.

主权项

1. A method of identifying a genetic mutation in a human small integral membrane protein of the lysosome/late endosome (“SIMPLE”) gene in a human subject, said method comprising:
(a) hybridizing a nucleic acid sequence of a coding region of a human small integral membrane protein of the lysosome/late endosome (“SIMPLE”) gene consisting of a coding portion of SEQ ID NO:1, or a naturally occurring sequence alteration thereof from a human subject with an oligonucleotide specific for a SIMPLE gene missense mutation, wherein the missense mutation alters the encoded amino acid sequence at a residue selected from the group consisting of amino acid residues 112, 115, and 116 of SEQ ID NO:2; and (b) detecting hybridization of the oligonucleotide with the nucleic acid sequence from the human subject; and (c) identifying a genetic mutation in the SIMPLE gene in the subject when hybridization is detected in step (b).