DISEASE INFORMATION
Mental retardation is one of the primary pediatric referrals, yet its etiology is frequently difficult to establish.¹ The prevalence of mental retardation in developed countries is estimated at 1-3%.² X-linked mental retardation (XLMR) affects mostly males at a prevalence of about 1 in 1000.² Female carriers often show milder symptoms due to skewed X-chromosome inactivation and other factors.¹ 

A recent study has implicated the SLC9A6 gene as a cause of X-linked mental retardation. Patients in this study showed clinical features characteristic of Angelman syndrome such as severe developmental delay, microcephaly, seizures, ataxia, and absent speech, nonetheless, all patients tested negative for 15q11-13 findings.³ Genetic analysis of the SCL9A6 gene may be indicated in male patients with a non-15q11-13 related Angelman syndrome phenotype, especially if X-linked inheritance is suspected.

TESTING BENEFITS & INDICATIONS
Genetic analysis of the SCL9A6 gene may be indicated in male patients with a non-15q11-13 related Angelman syndrome phenotype, especially if X-linked inheritance is suspected.³ Identification of a SLC9A6 mutation in a patient can help determine carrier status of females in the family and allows for prenatal diagnosis.

TEST DESCRIPTION
This Ambry Test is a gene sequence analysis performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 1-16 of the SLC9A6 gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns. Specific mutation analysis for individual SLC9A6 mutations known to be in the family is also available.

MUTATION DETECTION RATE
This test detects 99% of disease causing mutations in the SLC9A6 gene.

SPECIMEN REQUIREMENTS
Blood:Collect 3-5 cc from adult or 2 cc 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.
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.

REFERENCES
¹ Ropers HH & Hamel BCJ. Nat Rev Genet. 2005;6(1):46-57.
² Chiurazzi P et al. Eur J Hum Genet. 2008;6:422-434.
³ Gilfillan GD et al. Am J Hum Genet. 2008;82:1003-1010.

DISCLAIMER
This test was developed and its performance characteristics were determined by Ambry Genetics Corporation.  The laboratory is regulated under the Clinical Laboratory Improvement Amendments 2003 as qualified to perform nonwaived testing.  The Ambry Test: X-linked Angelman-like Syndrome (SLC9A6) analyzes the following types of mutations: nucleotide substitutions, small deletions, small insertions and small indels.  It is not intended to analyze the following types of mutations: gross deletions/duplications, gross rearrangements, deep intronic variations, and other unknown abnormalities.  The pattern of mutation types varies with the gene tested and the Ambry Test detects a high but variable percentage of known and unknown mutants of the classes stated.  A negative result from the analysis cannot rule out the possibility that the tested individual carries a rare unexamined mutation or mutation in the undetectable group.  The Ambry Test: X-linked Angelman-like Syndrome (SLC9A6) is designed and validated to be capable of detecting >99% of described mutations in SLC9A6 (considering less than 1% to be the other types of mutations).  X-linked mental retardation is a complex clinical disorder , which in most cases is not due to alterations in SLC9A6, cases due to alterations in this gene will generally be detected by the Ambry Test: X-linked Angelman-like Syndrome (SLC9A6) except as noted above.  Mutations in other genes or the regions not tested by the Ambry Test: X-linked Angelman-like Syndrome (SLC9A6) can also give rise to clinical conditions similar to Angelman-like syndrome/X-linked mental retardation. Although molecular tests are highly accurate, rare diagnostic errors may occur.  Possible diagnostic errors include sample mix-up, erroneous paternity identification, technical errors, clerical errors, and genotyping errors. Genotyping errors can result from trace contamination of PCR reactions, from maternal cell contamination in fetal samples, from rare genetic variants, which interfere with analysis, or from other sources. This report does not represent medical advice.  Any questions, suggestions, or concerns regarding interpretation of results should be forwarded to a genetic counselor, medical geneticist, or physician skilled in interpretation of the relevant medical literature.