XLMR 21: IL1RAPL1 Gene Sequencing

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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

Submit only 1 of the following specimen types

Preferred specimen type: Whole Blood

Type: Whole Blood

Specimen Requirements:

In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva

Specimen Requirements:

OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

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 Emory Genetics Laboratory, 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