Diagnostic Test Directory

Molecular Genetics Laboratory

CHOP in the News

Clinical Lab Products quotes Avni Santani, PhD, Scientific Director, Molecular Genetics Laboratory, in a story about next-gen sequencing. Read the story »

Laboratory Update

Testing for the Noonan spectrum of disorders is now available at the Molecular Genetics Laboratory. Learn more about Noonan spectrum testing »

Autism Spectrum of Disorders/Macrocephaly (PTEN)

    Collect

    Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA is also acceptable.

    Volume Required

    5 ml whole blood or 3 ug extracted DNA

    Minimum Required

    3 ml whole blood or 1 ug extracted DNA Please note: 1 ug of DNA will suff

    Transport

    Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.

    Stability

    Whole blood can be refrigerated until shipment.

    Unacceptable conditions

    Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.

    Specimen Handling

    Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.

Days Performed

Mon - Fri 9:00am to 4:00pm

Reported

4-6 weeks; known point mutation 2-3 weeks

CPT

Seq & Del/Dup: 81321, 81323; Sequence Only- 81321; Del/Dup Only- 81323; Known Point Mutation- 81322

Disease Information

Clinical Features:

Germline mutations in the PTEN gene have been identified in Cowden syndrome, Bannayan-Riley-Ruvalcaba Syndrome, Proteus syndrome and Proteus-like syndrome, now collectively referred to as PTEN Hamartoma Tumor Syndrome (PHTS). Cowden syndrome (CS-MIM 158350) is a multiple hamartoma syndrome with a high risk of breast, thyroid and endometrial cancer. Bannayan-Riley-Ruvalcaba Syndrome (BRRS-MIM 153480) is characterized by macrocephaly, intestinal hamartomatous polyposis, lipomas, and pigmented macules of the glans penis in males. Proteus syndrome (PS-MIM 176920) is a highly variable disorder involving disproportionate overgrowth of multiple tissues, as well as connective tissue nevi, epidermal nevi, and hyperostoses. Although PTEN is most recognized for its role in carcinogenesis, germline mutations in PTEN have been identified in children with autism and significant macrocephaly with a parent affected with CS or BRRS . Subsequently, additional studies have reported PTEN mutations in children affected with significant macrocephaly and autism.

Molecular Genetics:

The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) gene (MIM 601728) is a tumor suppressor gene located on chromosome 10q23.3. It functions as a dual-specificity phosphatase that is active in numerous pathways involved with cellular growth. Missense, nonsense, splice site mutations, indels and large deletions have been identified in this gene.

Test Methods:

We offer DNA sequence analysis and deletion/duplication testing of the entire coding region of the PTEN gene. These tests can be ordered as a panel or individually. PCR amplification and sequence analysis is performed on the coding exon including splice junctions. The patient’s gene sequence is compared to a reference sequence. Sequence variants are classified as mutations, variants of unknown significance or benign variants unrelated to disease. Variants of unknown significance may warrant further studies in the patient and other family members. Mutations in promoters, deep intronic regions and other regulatory regions will not be identified with this assay. Large deletions and duplications will be detected using multiplex ligation-dependent probe amplification assay (MLPA).

Detection Rate:

A number of studies have demonstrated that germline mutations in the PTEN gene are present in 10-20% of individuals with autism spectrum disorders and macrocephaly.

Results:

Test results with interpretation will be mailed and/or faxed to the referring physician or send out lab following completion of the test. Additional reports will be provided as requested.

Utility:

The clinical utility of the assay is to support a clinical diagnosis of the disease, facilitate genetic counseling, and assess the risk to other first degree relatives and to facilitate testing of at - risk family members.

Search Lab Test Directory

Search by disease or test name

View a full list of all lab tests

Contact Us

Ask for more information about our laboratory services.

215-590-5221