Submission Details

Autosomal recessive

01/14/2020

The FLVCR1 gene is located on chromosome 1 at 1q32.3 and encodes the FLVCR heme transporter 1 protein, a member of the major facilitator superfamily of transporter proteins which is specifically involved in the transmembrane transport of cytoplasmic heme. The protein plays a critical role in erythropoiesis by protecting the developing erythroid cells from heme toxicity. FLVCR1 was first reported in relation to autosomal recesssive posterior column ataxia-retinitis pigmentosa syndrome in 2010 (21070897: Rajadhyaksha et al. 2010). At least 11 unique variants (including missense and loss of function variants) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, segregation data and experimental evidence. Variants in this gene have been reported in at least seven probands in three publications (27923065: Chiabrando et al. 2016; 27353947: Tiwari et al. 2016; 30656474: Kuehlewein et al. 2019). Variants in this gene segregated with disease in two families. Clinical variability was noted with affected individuals presenting with either posterior column ataxia with retinitis pigmentosa (PCARP), non-syndromic retinitis pigmentosa, or hereditary sensory and autonomic neuropathy (HSAN). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. It is suggested that the underlying disease mechanism may be heme overload (27923065: Chiabrando et al. 2016). This gene-disease relationship is supported by expression studies and in vitro functional assays in patient and non-patient cells (21070897: Rajadhyaksha et al. 2010; 27923065: Chiabrando et al. 2016). In summary, FLVCR1 is definitively associated with autosomal recessive posterior column ataxia-retinitis pigmentosa syndrome.

27923065 30656474 27353947 21070897