Mutation of the PAFAH1B1 (17p13.3) gene, previously known as the LIS1 gene, cause PAFAH1B1-associated lissencephaly/subcortical band heterotopia. MDS is caused by deletions that include both the PAFAH1B1 and the YWHAE genes. ILS is caused by mutation of the PAFAH1B1 gene with ~68% of mutations being detected by deletion/duplication analysis and ~32% being detected by sequencing analysis.
Please note that lissencephaly and SBH are graded by anterior-posterior gradient and severity. When the lissencephaly or SBH is more severe posteriorly, it is referred to as a posterior to anterior (p>a) gradient. When more severe anteriorly, it is referred to as an anterior to posterior (a>p) gradient. PAFAH1B1 abnormalities generally give rise to a p>a gradient, whereas abnormalities of DCX generally give rise to an a>p gradient (GeneReviews). This testing is for the PAFAH1B1 gene only.
For patients with suspected PAFAH1B1-associated lissencephaly/subcortical band heterotopia, deletion/duplication analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by deletion/duplication analysis, full gene sequencing is appropriate.
Deletion/Duplication testing should be ordered as the first tier test.
- Confirmation of a clinical diagnosis of PAFAH1B1-Associated Lissencephaly/Subcortical Band Heterotopia in an individual in whom deletion/duplication analysis was negative.
- Carrier testing in adults with a family history of autosomal recessive PAFAH1B1-Associated Lissencephaly/Subcortical Band Heterotopia in whom deletion/duplication analysis was negative.
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.
- Deletion/duplication analysis of the PAFAH1B1 gene is available and is required before sequencing analysis.
- Both sequencing (SO) and deletion/duplication (SQ) analysis of the DCX gene is 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 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.