XLID, HUWE1-related: HUWE1 Gene Deletion/Duplication

Condition Description

Intellectual disability (ID) is a nonprogressive 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.

Syndromic X-Linked Mental Retardation, Turner Type
Missence mutations in the HUWE1 gene were identified in several families with a syndromic form of XLID.  The clinical presentation is variable with the ID ranging from moderate to profound.  Additional features that can be present include macrocephaly and speech/language delay or absent speech.  No dysmorphic features were reported. 

X-Linked Mental Retardation 17
Microduplications of chromosome Xp11.22, including both the HSD17B10 and the HUWE1 genes, cause a nonsyndromic form of X-linked intellectual disability (XLMR 17).  The intellectual disability is mild to moderate in severity.

For patients with suspected HUWE1-related XLID, 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:

Genes (1)

Indications

This test is indicated for:
  • Confirmation of a clinical diagnosis of HUWE1-related XLID in an individual in whom sequence analysis was negative.
  • Carrier testing in adults with a family history of HUWE1-related XLID in whom sequence analysis was negative.

Methodology

DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.

Detection

Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, 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
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 72 hours of collection. Do not freeze.
DNA, Isolated
DNA

Requirements
Microtainer
3µg
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.

Special Instructions

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.
  • Sequence analysis of the HUWE1 gene is available and is required before deletion/duplication analysis.  
  • 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