Identification of a mutation in TNRC18 in a patient with clinical features of Fazio‐Londe disease

Abstract

Key Clinical MessageFazio‐Londe disease and Brown‐Vialetto‐Van Laere syndrome are rare related neurological disorders. Although SLC52A3 and SLC52A2 that encode riboflavin transporters are their only known causative genes, many patients without mutations in these genes have been reported. Clinical and genetic data of a patient with features suggestive of Fazio‐Londe disease are presented. Neurological examination revealed significant involvement of cranial nerves and weakness in the lower extremities. Pontobulbar presentations were prominent. EDX study suggested motor neuronopathy. Hearing was normal. She was diagnosed with FL disease. Response to riboflavin supplementation was not favorable. The patient's pedigree suggested recessive inheritance. SLC52A3 and SLC52A2 were screened and mutations were not observed. Results of exome sequencing and segregation analysis suggested that a mutation in TNRC18 is a candidate cause of disease in the patient. The three dimensional structure of the TNRC18 protein was predicted and it was noted that its two conserved domains (BAH and Tudor) interact and that the valine residue affected by the mutation is positioned close to both domains. A mutation in TNRC18 is cautiously reported as the possible cause of FL disease in the patient. The finding warrants further inquiries on TNRC18 about which little is presently known.