Condition Description

Both deletions and point mutations in the IL1RAPL1 gene (Xp22.1-p21.3) have been associated with X-linked mental retardation (XLMR). Affected males usually have mild to severe nonsyndromic XLMR without other abnormalities, dysmorphic features, or neurological findings. Hyperactivity and self-aggressive behavior have been reported. Females in some families have been reported to have MR, while females in other families appear to be unaffected.

IL1RAPL1 may also be deleted in families with a contiguous gene deletion syndrome that includes MR, adrenal hypoplasia, Duchenne muscular dystrophy, and glycerol kinase deficiency.

For patients with suspected XLMR 21, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.

References:

  • Carrie et al. 1999. A new member of the IL-1 receptor family highly expressed in hippocampus and involved in X-linked mental retardation. Nature Genetics 23:25-31.
  • Nawara et al. 2008. Novel mutation of IL1RAPL1 gene in a nonspecific X-linked mental retardation (MRX) family. Am J Med Genet Part A 146A:3167-3172.
  • OMIM: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300143

Genes (1)

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Indications

This test is indicated for:

  • Confirmation of a clinical diagnosis of XLMR 21
  • Carrier testing in adult females with a family history of XLMR 21

Methodology

PCR amplification of 11 exons contained in the IL1RAPL1 gene is performed on the patient's genomic DNA. Direct sequencing of amplification products is performed in both forward and reverse directions, using automated fluorescence dideoxy sequencing methods. The patient's gene sequences are then compared to a normal reference sequence. Sequence variations are classified as mutations, benign variants unrelated to disease, or variations of unknown clinical significance. Variants of unknown clinical significance may require further studies of the patient and/or family members. This assay does not interrogate the promoter region, deep intronic regions, or other regulatory elements, and does not detect large deletions.

Detection

Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient's biochemical phenotype.

Analytical Sensitivity: ~99%

Specimen Requirements

When sample fails to meet the acceptable criteria, 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
8µg
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 24 hours of collection. Do not refrigerate or freeze.
Saliva
SLV

Requirements
Oragene™ Saliva Collection Kit
Orangene™ Saliva Collection Kit used according to manufacturer instructions. Please contact EGL for a Saliva Collection Kit for patients that cannot provide a blood sample.
Collection and Shipping
Please do not refrigerate or freeze saliva sample. Please store and ship at room temperature.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.

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.

  • Deletion/duplication analysis of the IL1RAPL1 gene by CGH array is available for those individuals in whom sequence analysis is negative.
  • A CGH array-based test for deletion/duplication analysis of 64 different X-linked intellectual disability genes is available (OL).
  • Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
  • Prenatal testing is available to adult females who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.

How to Order