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
- Confirmation of a clinical diagnosis of UBE2A-Related Syndromic XLMR.
- Carrier testing in adults with a family history of UBE2A-Related Syndromic XLMR.
Analytical Sensitivity: ~99%
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple 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.
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.