Methods for diagnosing scapuloperoneal spinal muscular atrophy or Charcot-Marie-Tooth disease type 2C by detecting mutations in TRPV4
The present invention provides methods, kits, and compositions for detecting mutations in transient receptor potential cation channel, subfamily V, member 4 (TRPV4). In particular, mutations are detected in TRPV4 to detect diseases such as scapuloperoneal spinal muscular atrophy (SPSMA) and hereditary motor and sensory neuropathy type IIC (HMSN IIC) or Charcot-Marie-Tooth disease type 2C (CMT2C).
1. A method of diagnosing a human subject with scapuloperoneal spinal muscular atrophy (SPSMA) and/or Charcot-Marie-Tooth disease type 2C (CMT2C) or identifying said subject as a carrier thereof, comprising:
(a) assaying a biological sample from said human subject to identify a thymine present at position 946 of exon 6 of the TRPV4 gene;
(b) assaying said biological sample from said human subject to identify an adenine present at position 806 of exon 5 of the TRPV4 gene; and
(c) diagnosing said human subject as having or being a carrier of:
(i) SPSMA based on the presence of said thymine present at position 946 of exon 6 of the TRPV4 gene, and/or
(ii) CMT2C based on the presence of said adenine present at position 806 of exon 5 of the TRPV4 gene.
2. The method of claim 1 , wherein said human subject is asymptomatic.
3. The method of claim 1 , wherein said human subject displays symptoms indicative of SPSMA and/or CMT2C.
4. The method of claim 1 , wherein assaying said sample utilizes a nucleic acid detection assay to determine the identity of the nucleotide at position 946 of exon 6 of the TRPV4 gene and the identity of the nucleotide at position 806 of exon 5 of the TRPV4 gene.
5. A method of diagnosing a human subject with scapuloperoneal spinal muscular atrophy (SPSMA) and/or Charcot-Marie-Tooth disease type 2C (CMT2C) or identifying said subject as a carrier thereof, comprising:
(a) assaying a biological sample from said human subject to identify a histidine present at position 269 of the TRPV4 protein;
(b) assaying a biological sample from said human subject to identify a cysteine present at position 316 of the TRPV4 protein; and
(c) diagnosing said subject as having or being a carrier of:
(i) CMT2C, based on the presence of said histidine present at position 269 of the TRPV4 protein, and/or
(ii) SPSMA, based on the presence of said cysteine present at position 316 of the TRPV4 protein.
6. The method of claim 5 , wherein said human subject is asymptomatic.
7. The method of claim 5 , wherein said human subject displays symptoms indicative of CMT2C and/or SPSMA.
8. The method of claim 5 , wherein assaying said sample utilizes a protein detection assay to detect TRPV4 proteins with said histidine amino acid at position 269 and/or said cysteine present at position 316.