On this page, you will find information about a genetic change that was identified in a UDN participant. We are trying to find others with the same or similar condition. (Sharing information on this website is not a requirement of UDN participation. Only descriptions about participants who give explicit consent will appear here.)

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Date of Report July 1, 2016
Full Gene Name Additional sex combs-like 2
Location Chromosome 2 (2p23.3)
Ideogram: ASXL2 gene on chromosome 2

Click to enlarge ideogram in new window (generated using the NCBI Genome Decoration Page )
Function The ASXL2 gene is the human homolog of the Drosophila asx gene. The asx gene enhances the function of a gene that codes for a protein involved in transcriptional activation and silencing (Katoh and Katoh, 2003 ).
Database Links GeneCards: GC02M025733 NCBI Gene: 55252 OMIM: 612991 UniProtKB/Swiss-Prot: Q76L83
Clinical Significance A change in the ASXL2 gene was identified in a UDN participant and other patients with similar symptoms (Shashi et al, 2016 ).
The participant, an 8-year-old male who is larger than average (macrosomia) and has atypical facial features (including a large birthmark on his forehead (glabellar hemangioma)), a decrease in brain white matter (cerebral white matter atrophy), learning difficulties, and mild developmental delays was found to carry the following de novo genetic variant in the ASXL2 gene: c.2424delC/p.P808fs.
Gene Inheritance Pattern Position Transcript DNA Change Protein Change
ASXL2 autosomal dominant chr2:25966781 NM_018263 c.2424delC p.P808fs
Since infancy, the patient’s height, weight and head circumference have been above the 95th percentile, and X-rays have shown advanced bone age. He had two heart problems (ventricular septal defect, patent ductus arteriosus) that resolved on their own. At age 5, he was diagnosed with weak cartilage in the walls of his trachea and bronchial tubes (tracheomalacia and bronchomalacia). Currently he has a slightly prolonged QT interval, sleep apnea, and elevated liver enzymes (transaminases).

The patient also has atypical facial features, including a large birthmark on his forehead (glabellar hemangioma), widely spaced eyes (hypertelorism), a flat nasal bridge, slightly downslanting eyes (palpebral fissures), and small ears. He also has multiple small birthmarks (capillary hemangiomas) on his chest, upper arms, and neck.

Developmentally, the patient has shown learning difficulties and had mild developmental delays.

Some of his other features include:

  • Mild accumulation of fat in the liver (mild hepatic steatosis)
  • Elevated liver enzymes (transaminases)
  • Seizures during fever (febrile seizures)
  • High insulin and lipid levels (hyperinsulinemia, hyperlipidemia)
  • Insulin resistance
  • Abnormal copper balance (abnormality of copper homeostasis)
  • Mild sleep apnea (obstructive)
  • Cupped and round ear
  • High palate
  • Skin of upper eyelid covers inner corner of eye (epicanthus)
  • Droopy eyes (ptosis)
  • Abnormality of the cornea (ovoid shaped corneas, horizontal>vertical)
  • Features of autism
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