PTEN-Related Disorders (including Autism Spectrum Disorder)
The Ambry Test: PTEN-Related Disorders detects approximately 99% of all described PTEN mutations. In order to offer flexible testing options, gene sequence analysis and deletion/duplication analysis of the PTEN gene are arranged as two separate tests.
PrintThe Ambry Test: PTEN-Related Disorders detects approximately 99% of all described PTEN mutations. In order to offer flexible testing options, gene sequence analysis and deletion/duplication analysis of the PTEN gene are arranged as two separate tests.
PTEN Hamartoma tumor syndrome (PHTS) encompasses the following syndromes:
Cowden Syndrome (CS) is a multiple hamartoma syndrome with a high risk of benign and malignant tumors of the thyroid, breast, and endometrium.
Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare congenital disorder characterized by macrocephaly, lipomatosis, hamartomatous intestinal polyposis, and pigmented penile macules.
Proteus syndrome (PS) is a variable disorder involving disproportionate overgrowth of multiple tissues and body parts.
Autism Spectrum Disorder (ASD) is a common developmental disorder involving impairments in language and social interaction. Affecting 1 in 110 children, approximately 10% of ASD cases are due to genetic causes, and PTEN mutations are specifically associated with autism cases accompanied by macrocephaly.
CS is a multiple hamartoma syndrome with a high risk of developing tumors of the thyroid, breast, and endomentrium. Mucocutaneous lesions, thyroid abnormalities, fibrocystic disease, multiple uterine leiomyoma, and macrocephaly can also be seen.1,2 Affected individuals have a lifetime risk of up to 50% for breast cancer, 10% for thyroid cancer, and 5-10% for endometrial cancer.2 Over 90% of individuals with CS will express some clinical manifestation by their 20’s.1
BRRS is a congenital disorder characterized by macrocephaly, lipomatosis, hamartomatous intestinal polyposis, and pigmented penile macules.3
PS is a complex, highly variable disorder involving congenital malformations and disproportionate over growth of multiple tissues and body parts.4
ASD is a developmental disorder involving impairments in language and social interaction skills. It affects 1 in 110 children, and approximately 10% of ASD cases are due to genetic causes. PTEN mutations are specifically associated with autism cases accompanied by macrocephaly.5,6
PTEN is a suppressor gene which mediates cell cycle arrest and apoptosis. Mutations are inherited in an autosomal dominant manner. Mutations in PTEN are classified under the PTEN Hamartoma Tumor Syndrome (PHTS) which encompasses several syndromes including Cowden Syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Autism Spectrum Disorder (ASD).1
Due to the increase risk for malignancies associated with PHTS, genetic testing is recommended for at-risk patients. Increased cancer surveillance and assessments of prophylactic treatment are available for those who carry PTEN mutations. PTEN testing is also recommended for individuals diagnosed with Lhermite-Duclos disease, even in the absence of other signs of PHTS. Moreover, the American College of Medical Genetics has included PTEN testing as part of their diagnostic evaluation for Autism Spectrum Disorder.6
Mutations in the PTEN gene can be found in approximately 85% of individuals with CS, 65% of individuals with BRRS, and 20% of individuals with PS. Furthermore, gross deletions have been found in 10% of individual with BRRS and/or CS-like syndrome.7 Mutations have also been reported in 8% of ASD patients and another 12% of patients diagnosed with developmental delay or mental retardation.8
Ambry Genetic employs two methods for the analysis of the PTEN gene:
Gene sequence analysis utilizes PCR-based sequencing in the sense and antisense directions for exons 1-9 of the PTEN gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns and the 5’UTR promoter region.
The Ambry Test: PTEN-related deletion/duplication analysis detects gross deletions/duplications using a MLPA kit.
Specific mutation analysis is also available for individual PTEN mutations identified in a family
Blood: Collect 3-5cc from adult or 2cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Call for availability.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 μg in TE at 50-100 ng/μl. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 2100 | PTEN Gene Sequence Analysis | 83891x1, 83894x12, 83898x11, 83904x22, 83909x22, 83912x1 |
| 2104 | PTEN Deletion / Duplication Only | 83891x1, 83894x1, 83900x1, 83901x23, 83909x1, 83912x1 |
| 2106 | PTEN Sequencing and Deletion / Duplication | 83891x1, 83894x12, 83898x11, 83904x22, 83900x1, 83901x23, 83909x23, 83912x2 |
| Technique | Days |
|---|---|
| PTEN Gene Sequence Analysis | 7-21 |
| PTEN Deletion / Duplication Only | 7-14 |
| PTEN Sequencing and Deletion / Duplication | 7-21 |
1 Eng C. J Med Genet . 2000;37:828-830.
2 Starink TM, van der Veen JPW, Arwert F, et al. Clin Genet. 1986;29:222–233.
3 Gorlin RJ, Cohen MM, Condon LM, Burke BA. Am J Med Genet 1992;44:307–314.
4 Cohen MM Jr. Am J Med Genet C Semin Med Genet. 2005;137C(1):38-52.
5 Butler MG, Dasouki MJ, Zhou XP, et al. J Med Genet. 2005;42:318–321.
6 Herman GE, Henninger N, Ratliff-Schaub K, et al. Genet Med. 2007; 5:268-74.
7 Zhou XP, Waite KA, Pilarski R, et al. Am J Hum Genet. 2003;73(2):404-11.
8 Varga EA, Pastore MS, Prior T et al. Gene in Med. 2009;11:111-117.