UBE2A-related Syndromic XLMR: UBE2A Gene Sequencing

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Condition Description

Intellectual disability (ID) is a non-progressive cognitive impairment affecting 1-3% of the Western population. It is estimated that up to 50% of moderate-severe cases have genetic causes and approximately 10% are due to X-linked intellectual disability disorders (XLID). XLID can be syndromic or nonsyndromic and is observed in all ethnic groups. More than 100 XLID syndromes have been described in the literature to date. Fragile X is the most common XLID syndrome (~1 in 4000 males) while others can be quite rare with only a few patients reported in the literature. Males can have moderate to severe intellectual disability depending on the syndrome, and carrier females can also be affected, but typically have milder clinical symptoms.

Rafaella et al. (2006) describe a family in which three males from two generations had syndromic intellectual disability.  Chromosome analysis and fragile X testing were normal.   In addition to intellectual disability, all three of the affected family members had hair whorls, up-slated palpebral fissures, large mouth with down-turned corners and thin lips, short, broad neck, low posterior hairline, widely spaced nipples, small penis, marked generalized hirsutism, dry skin, seizures, and severe speech impairment.   Their carrier mothers were clinically unaffected with completely skewed X inactivation in leukocytes.  A nonsense mutation in the UBE2A gene (Xq24-q25) was found in affected and carrier individuals and was absent in an unaffected female who had a random X inactivation pattern.

For patients with suspected UBE2A-Related Syndromic XLMR, 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.

  • Rafaella et al. (2006) Am J Hum Gen 79:549-555.
  • OMIM #312180: UBE2A gene

Genes (1)


This test is indicated for:
  • Confirmation of a clinical diagnosis of UBE2A-Related Syndromic XLMR.
  • Carrier testing in adults with a family history of UBE2A-Related Syndromic XLMR.


PCR amplification of 6 exons contained in the UBE2A 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.


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 clinical and/or 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

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.

  • Deletion/duplication analysis of the UBE2A gene by CGH array is available for those individuals in whom sequence analysis is negative.
  • 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 only for known familial mutations to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.
  • X-Linked Intellectual Disability panels are available for 30, 60, and 90 genes.

How to Order