Methods for diagnosing autism spectrum disorders

• US 9,834,819 B2
• Filed: 03/17/2014
• Issued: 12/05/2017
• Est. Priority Date: 09/08/2009
• Status: Expired due to Fees

• Current Assignee: Laboratory Corporation Of America Holdings
• Original Assignee: Laboratory Corporation Of America Holdings
• Inventors: Margulies, David Michael, Bear, Mark Firman
• Primary Examiner(s): Mahatan, Channing S
• Application Number:
  US14/215,875
• Publication Number:
  US 20140186839A1
• Time in Patent Office: 1,359 Days
• Field of Search: None
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/178 miRNA, siRNA or ncRNA

Abstract

The invention generally relates to methods for diagnosing autism spectrum disorders. In certain embodiments, the invention provides a method for diagnosing presence or increased risk of developing an autism spectrum disorder in a subject.

Claims

1. A method for detecting a mutation associated with the presence or an increased risk of developing an autism spectrum disorder in a subject, the method comprising:

obtaining a nucleic acid from a tissue or body fluid sample from a subject;

conducting an assay to identify a HOMER 1 c.195G>

T, M65I variant sequence in the nucleic acid;

conducting an assay to identify a HOMER 1 c.290C>

T, S97L variant sequence in the nucleic acid; and

conducting an assay to identify a HOMER 1 c.425C>

T, P142L variant sequence in the nucleic acid.

2. The method according to claim 1, wherein the assay comprises at least one of nucleic acid sequencing, hybrid capture, and epigenetic analysis.

3. The method according to claim 1, further comprising conducting an assay to identify an additional variant sequence in at least one of a TSC1, TSC2, MECP2, SHANK3, GRM1, GRM5, ARC, EIF4E, HOMER1, HRAS, MAP2K1, MAP2K2, RAF1, PIK3CA, PIK3R1, FMR1, PTEN, RHEB or UBE3A gene.

4. The method of claim 3, wherein the nucleic acid in the conducting step comprises a gene, an exon, an intron, a gene regulatory element, an expressed RNA, an siRNA, or an epigenetic element.

5. The method according to claim 3, wherein the variant comprises at least one of the following mutations:

GRM5 c.3503T>

C, L1168P;

MAPK2 c.581-1G>

T;

HRAS c.383G>

A, R128Q;

a MECP2 c.1477G>

T, E483X.

6. The method according to claim 1, further comprising conducting an assay to identify an additional variant sequence in at least one of a TSC1, TSC2, SHANKS3, or HOMER1 gene.

7. The method according to claim 2, wherein the nucleic acid sequencing comprises at least one of single-molecule sequencing-by-synthesis or massively parallel sequencing.

8. The method according to claim 2, wherein the nucleic acids from individual subjects are combined and analyzed as a pooled sample to identify at least one nucleic acid that shows a variation.

9. The method according to claim 8, wherein a plurality of the pooled samples are analyzed to identify at least one nucleic acid that shows the same variation in at least two pooled samples.

10. The method according to claim 1, wherein the autism spectrum disorder comprises at least one of non-syndromic autism, classical autism, Asperger'"'"'s syndrome, Rett'"'"'s syndrome, childhood disintegrative disorder, or pervasive developmental disorder not otherwise specified (PDD-NOS).

11. The method according to claim 1, wherein the autism spectrum disorder comprises non-syndromic autism.

12. The method according to claim 1, wherein the subject is a child.

13. The method according to claim 1, wherein the subject is a fetus.

14. The method according to claim 1, wherein the body fluid comprise at least one of cerebrospinal fluid, blood, amniotic fluid, maternal blood, and urine.