Method for diagnosing autism spectrum disorder
The present invention provides methods of diagnosing and/or predicting autism spectrum disorder comprising determining the presence of microdeletions and microduplications on chromosomes 15 and 16.
1. A method for genetic analysis, comprising:
using a multiplex ligation probe amplification (MLPA) assay to assess a nucleic acid sample from a human individual or human fetus for the presence of:
a microduplication of about 2.0 Mb in chromosome region 15:28.719-30.701 Mb;
a microdeletion of about 1.7 Mb in chromosome region 15:28.709-30.405 Mb;
a microdeletion or microduplication of at least two genes selected from the group consisting of: MTMR15, MTMR10, TRPM1, KLF13, OTUD7A, CHRNA7 and hsa-mir-211 in chromosome region 15q13.2-13.3; or
a microduplication of about 0.5 Mb in chromosome region 15:28.902-29.404 Mb;
wherein the MLPA assay comprises combining the nucleic acid sample with MLPA probes that are complementary to the chromosomal region that is assessed.
2. The method of claim 1 , wherein:
the microduplication of about 2.0 Mb or the microdeletion of about 1.7 Mb comprises the MTMR15, MTMR10, TRPM1, KLF13, OTUD7A, CHRNA7 and hsa-mir-211 genes; or
the microduplication of about 0.5 Mb comprises the MTMR15, MTMR10, TRPM1 and has-mir-211 genes.
3. A method for genetic analysis of a nucleic acid sample from a human individual or human fetus, comprising:
detecting, using a MLPA assay, a microduplication of at least two genes selected from the group consisting of: MTMR15, MTMR10, TRPM1, KLF13, OTUD7A, CHRNA7 and hsa-mir-211 in chromosome region 15q13.2-13.3;
wherein the MLPA assay comprises combining the nucleic acid sample with MLPA probes that are complementary to the at least two genes.
4. The method of claim 3 , wherein:
the microduplication includes MTMR15, MTMR10, TRPM1 and has-mir-211; or
the microduplication includes MTMR15, MTMR10, TRPM1, KLF13, OTUD7A, CHRNA7 and hsa-mir-211.
5. The method of claim 1 , wherein the MLPA assay comprises:
using at least one MLPA probe for each of the MTMR15, TRPM1, OTUD7A and CHRNA7 genes; or
using at least one MLPA probe for each of the MTMR15, MTMR10 and TRPM1 genes.
6. The method of claim 5 , wherein the MLPA assay comprises using at least one MLPA probe for each of the MTMR15, TRPM1, OTUD7A and CHRNA7 genes.
7. The method of claim 1 , wherein the method further comprises sequencing a PCR product amplified by the MLPA assay.
8. The method of claim 1 , wherein the human individual or human fetus is suspected of having an autism spectrum disorder.
9. The method of claim 1 , wherein the human individual or human fetus has a family history of autism spectrum disorder.
10. The method of claim 1 , wherein the human individual was previously diagnosed with autism spectrum disorder using symptomatic diagnostic criteria.
11. The method of claim 1 , comprising detecting the about 1.7 Mb microdeletion.