Neurodegeneration due to Cerebral Folate Transport Deficiency: FOLR1 Gene Deletion/Duplication

Condition Description

Loss-of-function mutations in the FOLR1 gene (11q13.4) cause an inherited disorder of brain-specific folate deficiency.  The FOLR1 gene encodes the folate receptor alpha (FRα), one of two GPI-anchored receptors that mediate cellular uptake of 5-methyltetrahydrofoloate (MTHF).  Mutations in the FOLR1 gene impair the cerebral folate transport function.  Features of this autosomal recessive disorder begin in late infancy and include severe developmental regression, movement disturbances, epilepsy, and leukodystrophy.

For patients with suspected neurodegeneration due to cerebral folate transport deficiency, 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.

  • Steinfeld et al. (2009). Am J Hum Genet, 85:354-363.
  • OMIM #613068: Neurodegeneration due to cerebral folate transport deficiency
  • OMIM #136430: FOLR1 gene

Genes (1)

Your search may have returned a result for a gene alias. Click here for a full list of genes and their aliases.


This test is indicated for:
  • Confirmation of a clinical diagnosis of neurodegeneration due to cerebral folate transport deficiency in an individual in whom sequence analysis was negative.
  • Carrier testing in adults with a family history of neurodegeneration due to cerebral folate transport deficiency in whom sequence analysis was negative.


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 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 (
Submit only 1 of the following specimen types
DNA, Isolated

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.
Whole Blood (EDTA)

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.

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 FOLR1 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.

How to Order