Welcome to the Gene Scene! Each week, we will explore a gene from the ACMG Secondary Findings list—genes identified by the American College of Medical Genetics and Genomics as having clear, actionable health implications.These genes are included because they’re linked to serious but preventable or manageable conditions when identified early. Here, we focus on the condition that led to the gene’s inclusion on the list, providing clear, relevant information that supports your clinic. To subscribe to the Gene Scene, contact your local GSL or send a request to info@ambrygen.com. 

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GENE SCENE SPOTLIGHT: This gene is not on the ACMG Secondary Findings List, but has been in the news due to the FDA releasing statements about treatment for patients with autism.

Clinical Phenotype Summary: 

The folate receptor 1 (FOLR1) gene is located on chromosome 11q13.4 and encodes the adult folate receptor 1, or folate-binding protein (OMIM_136430). Alterations in the FOLR1 gene are inherited in an autosomal recessive fashion in association with a cerebral folate transport deficiency. 

Cerebral Folate Transport Deficiency is characterized by:
•    Severe developmental regression
•    Psychomotor regression
•    Spastic paraplegia
•    Cerebellar ataxia and dyskinesia
•    Epilepsy
•    Leukodystrophy within late infancy 

Unique Considerations: 
•    Low CSF levels of 5-methyltetrahydrofolate (5MTHF) concentration and normal blood folates are observed in these patients. 
•    While there are no technical limitations for analysis of the FOLR1 gene on exome, biallelic variants in this gene would be reported if there was phenotypic overlap with the autosomal recessive condition Cerebral Folate Transport Deficiency.
     o    Monoallelic variants in this gene would not be reported for individuals with non-syndromic or isolated autism.
•    Questions about treatment for this individuals with a mutation in FOLR1?: Is there a medication to treat autism? | Children's Hospital of Philadelphia  
•    Additional information about this condition can be found on: GeneReviews FOLR1

To read more about Ambry’s research on this gene. Visit the Our Research dropdown on our website https://www.ambrygen.com/science.  

Citations: 
•    Perez-Duenas B, et al. (2010) J Inherit Metab Dis 33:795-802. PMID: 20857335
•    Steinfeld R, et al. (2009) Am J Hum Genet 85:354-363. PMID: 19732866

Ambry Genetics Gene-Disease Validity Scheme

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