Detecting and treating dementia
This document relates to methods and materials for detecting mutations that can be linked to dementia. For example, methods and materials for detecting one or more mutations within PGRN nucleic acid are provided. This document also provides methods and materials for detecting the level of progranulin expression. In addition, this document relates to methods and materials for treating mammals having a neurodegenerative disorder (e.g., dementia). For example, methods and materials for increasing PGRN polypeptide levels in mammals are provided, as are methods and materials for identifying agents that can be used to increase PGRN polypeptide levels in mammals.
1. A method for assisting in the identification of frontotemporal dementia, wherein said method comprises:
(a) performing an amplification reaction using a nucleic acid sample obtained from a human suspected of having dementia to amplify at least a portion of a PGRN nucleic acid sequence of said human to obtain amplified PGRN nucleic acid comprising a mutation as compared to the nucleic acid sequence set forth in SEQ ID NO:2, wherein said mutation is (i) a frameshift mutation or (ii) a mutation that results in the premature termination of the coding sequence of a PGRN polypeptide through the introduction of a stop codon,
(b) performing a sequencing reaction using said amplified PGRN nucleic acid to detect the presence of said mutation within said amplified PGRN nucleic acid, and
(c) classifying said human as having said mutation and frontotemporal dementia.
2. The method of claim 1 , wherein said nucleic acid sample is a cDNA sample.
3. The method of claim 1 , wherein said nucleic acid sample is a genomic DNA sample.
4. The method of claim 1 , wherein said mutation is a frameshift mutation.
5. The method of claim 4 , wherein said frameshift mutation is selected from the group consisting of p.Asp22fs, p.Cys31fs, p.Gly35fs, p.Thr52fs, p.Gly79fs, p.Val121fs, p.Pro127fs, p.Gln130fs, p.Cys157fs, p.Pro166fs, p.Ser226fs, p.Ala237fs, mutations.
6. The method of claim 1 , wherein said mutation is a mutation that results in the premature termination of the coding sequence of a PGRN polypeptide through the introduction of a stop codon.
7. The method of claim 6 , wherein said mutation is selected from the group consisting of p.Ser116X, p.Gln125X, p.Cys253X, p.Trp304X, p.Cys314X, p.Trp386X, p.Gln401X, p.Gln415X, p.Arg418X, and p.Arg493X mutations.
8. The method of claim 1 , wherein said method comprises providing a medical professional information about the detection of said presence of said mutation.
9. The method of claim 8 , wherein said method comprises placing said information on a computer database accessible to said medical professional.
10. A method for assisting in the identification of a risk for developing frontotemporal dementia, wherein said method comprises:
(a) performing an amplification reaction using a nucleic acid sample obtained from a human to amplify at least a portion of a PGRN nucleic acid sequence of said human to obtain amplified PGRN nucleic acid comprising a mutation as compared to the nucleic acid sequence set forth in SEQ ID NO:2, wherein said mutation is (i) a frameshift mutation or (ii) a mutation that results in the premature termination of the coding sequence of a PGRN polypeptide through the introduction of a stop codon,
(b) performing a sequencing reaction using said amplified PGRN nucleic acid to detect the presence of said mutation within said amplified PGRN nucleic acid, and
(c) classifying said human as having said mutation and as being at risk of developing frontotemporal dementia.
11. The method of claim 10 , wherein said nucleic acid sample is a cDNA sample.
12. The method of claim 10 , wherein said nucleic acid sample is a genomic DNA sample.
13. The method of claim 10 , wherein said mutation is a frameshift mutation.
14. The method of claim 13 , wherein said frameshift mutation is selected from the group consisting of p.Asp22fs, p.Cys31fs, p.Gly35fs, p.Thr52fs, p.Gly79fs, p.Trp304fs, p.Gly333fs, p.Cys366fs, p.Thr382fs, p.Ala412fs, p.Val452fs, and p.Cys466fs mutations.
15. The method of claim 13 , wherein said mutation is selected from the group consisting of p.Ser116X, p.Gln125X, p.Cys253X, p.Trp304X, p.Cys314X, p.Trp386X, p.Gln401X, p.Gln415X, p.Arg418X, and p.Arg493X.
16. The method of claim 10 , wherein said mutation is a mutation that results in the premature termination of the coding sequence of a PGRN polypeptide through the introduction of a stop codon.
17. The method of claim 10 , wherein said method comprises providing a medical professional information about the detection of said presence of said mutation.
18. The method of claim 17 , wherein said method comprises placing said information on a computer database accessible to said medical professional.