In 2003, Graham et al. reported two brothers with a unique clinical presentation and mutations in the IGBP1 gene (Xq13.1-q13.3), also called the Alpha 4 gene.
The brothers had a clinical presentation of coloboma (iris in one brother and optic nerve in the other), high forehead, severe retrognathia, mild to moderate intellectual disability, and agenesis of the corpus callosum (ACC). They also had low-set cupped ears with sensorineural hearing loss, downslanting palpebral fissures, short broad neck, pectus excavatum, scoliosis, and short stature. One brother also had choanal atresia and cardiac defects (ventricular septal defect and patent ductus arteriosis).
Changes in the 5’ UTR sequence of the IGBP1 gene were identified in these brothers and their carrier mother. The changes were not observed in the brothers’ maternal half-uncle or in 410 control chromosomes. The protein product of the IGBP1 gene has been shown to interact with MID1, the product of the gene mutated in X-linked Opitz GBBB syndrome.
For patients with suspected XLMR with agenesis of the corpus callosum, 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.
- Graham, JM et al. A new X-linked syndrome with agenesis of the corpus callosum, mental retardation, coloboma, micrognathia, and a mutation in the Alpha 4 gene at Xq13. Am J Med Gen 2003; 123A:37-44.
- OMIM #300472 Corpus Callosum, Agenesis of, with Mental Retardation, Ocular Coloboma, and Micrognathia
This test is indicated for:
- Confirmation of a clinical diagnosis of X-linked agenesis of the corpus callosum with mental retardation, coloboma, and micrognathia
- Carrier testing in adult females with a family history of X-linked agenesis of the corpus callosum with mental retardation, coloboma, and micrognathia
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%
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.
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.
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 IGBP1 gene by CGH array is available for those individuals in whom sequence analysis is negative.
- An XLID sequencing panel and a CGH array-based test for deletion/duplication analysis of 90+ different X-linked intellectual disability genes are available.
- 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 for known familial mutations only. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.