Angelman-like Syndrome: SLC9A6 Gene Deletion/Duplication

Condition Description

Mutations in the gene SLC9A6 (Xq26.3) lead to an X-linked mental retardation syndrome associated with microcephaly, seizures, ataxia, and absent speech. Many identified patients also display a happy demeanor with frequent smiling and spontaneous laughter reminiscent of Angelman syndrome. Affected individuals appear normal at birth, then display deceleration of head growth in the first year of life and a thin body habitus. Seizures typically begin to occur around 1-2 years of age. Many individuals have a happy demeanor with frequent smiling and episodes of unprovoked laughter. There is an absence of expressive language and profound mental retardation, along with ataxia and eye squint. Other possible features include an open mouth with profuse drooling, swallowing difficulties, hyperkinetic movements, and facial features such as a long, narrow face and pointed jaw. The clinical spectrum of features seems to resemble Angelman syndrome in younger patients and Christianson syndrome in older patients. There appears to be range of carrier phenotypes in carrier females, from mental retardation to absence of symptoms.

The SLC9A6 gene encodes the Na+/H+ exchanger protein NHE6. NHE6 is a membrane protein found in early recycling endosomal membranes and transiently associates with the plasma membrane. It is believed to have a role in regulating the lumen pH, and a consequence of NHE6 inactivity could be lowered endosomal pH and decreased monovalent ion content, both of which might affect protein folding and trafficking. The disruption in recycling endosome trafficking is likely to disturb the growth of dendritic spines during long-term potentiation, which is the process involved in memory and learning. Abnormalities in synaptic development and plasticity have also been shown to be involved in the pathogenesis of Angelman syndrome; UB3A is involved in the intracellular protein-processing apparatus at the level of protein ubiquination.

(Taken from Gilfillan, G. et al. SLC9A6 Mutaitons Cause X-Linked Mental Retardation, Microcephaly, Epliepsy, and Ataxia, a Phenotype Mimicking Angelman Syndrome. Am J Hum Gen 82:1003-1010, 2008.

Genes (1)

Indications

This test is indicated for male individuals with an Angelman-like phenotype who have tested negative for 15q11-13 findings and for MECP2 mutations.

Methodology

DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.

Detection

Detection is limited to duplications and deletions. Array CGH will not detect point mutations or intronic mutations. Results of molecular analysis must interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
DNA, Isolated
DNA

Requirements
Microtainer
3µg
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.
Whole Blood (EDTA)
WBP

Requirements
EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.

Special Instructions

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition. Please submit copies of previous test results (i.e. Angelman testing, Rett testing)
  • SLC9A6 Full Gene Sequencing (PQ) is also available.
  • X-Linked Intellectual Disability panels are available for 30, 60, and 90+ genes.
  • Prader-Willi/Angelman Methylation Studies (PW).
  • Rett Syndrome Sequencing of Methyl CpG-Binding Protein (MECP2) Gene (SR).
  • X-Linked Mental Retardation Deletion/Duplication Array CGH (OL).

How to Order