US 5,691,144 A · Methods of detecting novel mutations relating to X-linked Charcot-Marie-Tooth disease

Abstract

Specific mutations in the connexin-32 gene that are associated with X-linked Charcot-Marie-Tooth (CMT) disease are disclosed. Methods of diagnosing X-linked CMT disease are also disclosed. Methods include hybridization analysis, such as Southern or Northern analysis, which use hybridization of mutant connexin-32 nucleic acid probes to connexin-32 genes; direct mutation analysis by restriction digest; sequencing of the connexin-32 gene; hybridization of an allele-specific oligonucleotide with amplified genomic DNA; or identification of mutant connexin-32 proteins. Mutant connexin-32 nucleic acid probes are also disclosed. The mutant connexin-32 nucleic acid probes have a mutation in at least one of the following codons: 12, 26, 28, 44, 75, 86, 100, 103, 107, 124, 142, 154, 157, 160, 161, 172, 179, 181, 183, 185, 187, 198, 204, 205, 219, 230 and 235. Mutant connexin-32 nucleic acid probes having more than one of the mutations described above are also described, as are mutant connexin-32 nucleic acid probes having other mutations in addition to at least one mutation as described above. Isolated, mutant connexin-32 proteins encoded by mutant connexin-32 genes, as well as antibodies specific for the mutant connexin-32 proteins, are also disclosed.

Claims15

Dependent claims

A method of diagnosing X-linked Charcot-Marie-Tooth disease in an individual, comprising detecting a mutation in the connexin-32 gene of the individual, the mutation being in at least one codon selected from the group consisting of:

28, 44, 86, 100, 103, 124, 154, 157, 160, 161, 179, 181, 183, 187, 198, 204, 205, 219, 230 and 235, wherein the presence of the mutation in the connexin-32 gene is indicative of X-linked Charcot-Marie-Tooth disease.

A method of diagnosing X-linked Charcot-Marie-Tooth disease in an individual, comprising detecting the presence of a mutation in the connexin-32 gene of the individual, the mutation being selected from the group consisting of:

a change in the nucleic acid sequence of codon 12 from GGC to GGT;
a change in the nucleic acid sequence of codon 28 from ATC to AAC;
a change in the nucleic acid sequence of codon 44 from TGG to TTG;
a change in the nucleic acid sequence of codon 75 from CGG to TGG;
a change in the nucleic acid sequence of codon 86 from ACC to TCC;
a change in the nucleic acid sequence of codon 100 from CAC to TAC;
a change in the nucleic acid sequence of codon 103 from AAG to GAG;
a change in the nucleic acid sequence of codon 124 from AAG to AG;
a change in the nucleic acid sequence of codon 142 from CGG to CAG;
a change in the nucleic acid sequence of codon 154 from TAT to TAA;
a change in the nucleic acid sequence of codon 157 from TAC to TGC;
a change in the nucleic acid sequence of codon 160 from TAT to CAT;
a change in the nucleic acid sequence of codon 161 from GCC to GCT;
a change in the nucleic acid sequence of codon 172 from CCC to CTC;
a change in the nucleic acid sequence of codon 179 from TGC to CGC;
a change in the nucleic acid sequence of codon 181 from GTG to ATG;
a change in the nucleic acid sequence of codon 183 from CGC to TGC;
a deletion of codon 185;
a change in the nucleic acid sequence of codon 187 from AAA to GAA;
a change in the nucleic acid sequence of codon 198 from TCT to TTT;
a change in the nucleic acid sequence of codon 204 from CTC to GTC;
a change in the nucleic acid sequence of codon 205 from AAT to AGT;
a change in the nucleic acid sequence of codon 219 from CGC to TGC;
a change in the nucleic acid sequence of codon 230 from CGC to TGC;
and
a change in the nucleic acid sequence of codon 235 from TTC to TGC,
wherein the presence of a mutation in the connexin-32 gene is indicative of X-linked Charcot-Marie-Tooth disease.

24 more elements

A method of diagnosing X-linked Charcot-Marie-Tooth disease in an individual, comprising the steps of:

a. obtaining from the individual a test sample of DNA containing the connexin-32 gene;
b. examining the test sample for the presence of a mutation in the connexin-32 gene, the mutation being selected from the group consisting of:
a change in the nucleic acid sequence of codon 12 from GGC to GGT;
a change in the nucleic acid sequence of codon 28 from ATC to AAC;
a change in the nucleic acid sequence of codon 44 from TGG to TTG;
a change in the nucleic acid sequence of codon 75 from CGG to TGG;
a change in the nucleic acid sequence of codon 86 from ACC to TCC;
a change in the nucleic acid sequence of codon 100 from CAC to TAC;
a change in the nucleic acid sequence of codon 103 from AAG to GAG;
a change in the nucleic acid sequence of codon 124 from AAG to AG;
a change in the nucleic acid sequence of codon 142 from CGG to CAG;
a change in the nucleic acid sequence of codon 154 from TAT to TAA;
a change in the nucleic acid sequence of codon 157 from TAC to TGC;
a change in the nucleic acid sequence of codon 160 from TAT to CAT;
a change in the nucleic acid sequence of codon 161 from GCC to GCT;
a change in the nucleic acid sequence of codon 172 from CCC to CTC;
a change in the nucleic acid sequence of codon 179 from TGC to CGC;
a change in the nucleic acid sequence of codon 181 from GTG to ATG;
a change in the nucleic acid sequence of codon 183 from CGC to TGC;
a deletion of codon 185;
a change in the nucleic acid sequence of codon 187 from AAA to GAA;
a change in the nucleic acid sequence of codon 198 from TCT to TTT;
a change in the nucleic acid sequence of codon 204 from CTC to GTC;
a change in the nucleic acid sequence of codon 205 from AAT to AGT;
a change in the nucleic acid sequence of codon 219 from CGC to TGC;
a change in the nucleic acid sequence of codon 230 from CGC to TGC;
and
a change in the nucleic acid sequence of codon 235 from TTC to TGC,
wherein the presence of a mutation in the connexin-32 gene is indicative of X-linked Charcot-Marie-Tooth disease.

26 more elements

A method of diagnosing X-linked Charcot-Marie-Tooth disease in an individual, comprising the steps of:

a. obtaining from the individual a test sample of DNA comprising the connexin-32 gene of interest;
b. determining the nucleic acid sequence of all or a fragment of the connexin-32 gene of interest;
and
c. comparing the nucleic acid sequence of the connexin-32 gene of interest or the fragment of the connexin-32 gene of interest to SEQ ID NO. 1,
wherein the presence of a mutation in the connexin-32 gene of interest or fragment of the connexin-32 gene of interest, as compared to SEQ ID NO. 1, the mutation being in at least one codon selected from the group consisting of:
28, 44, 86, 100, 103, 124, 154, 157, 160, 161, 179, 181, 183, 187, 198, 203, 205, 219, 230 and 235, is indicative of X-linked Charcot-Marie-Tooth disease.

3 more elements

Dependencies are inferred from the claim text.

Methods of detecting novel mutations relating to X-linked Charcot-Marie-Tooth disease

Life of this patent

Methods of detecting novel mutations relating to X-linked Charcot-Marie-Tooth disease

Life of this patent

Abstract

Claims15