Clinical phenotypes caused by BCS1L pathogenic mutations vary greatly. Phenotypes of the disease can range from mild, like that of Björnstad syndrome, which is characterized by pili torti (abnormally flat, twisted hair shafts), to severe, like that of GRACILE syndrome, which is characterized by growth restriction, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death.

Additionally, BCS1L pathogenic mutations have been related to an unidentified complex III deficiency, a disorder characterized by hypotonia, renal and hepatic diseases, and developmental delays. According to studies reviewed so far, the homozygous p.Ser78Gly variation in the BCS1L gene was present in every patient with GRACILE syndrome.

A child 24 days old had the classic clinical pattern of GRACILE syndrome. A missense mutation (c.245C > T, p.Ser82Leu) and a minor deletion (c.231_232delCA, p. Ser78Cysfs*9) in the BCS1L gene, both acquired from his father and mother individually, were discovered by whole exome sequencing in the patient, he passed away at the age of 5 months. Two unique variations in the BCS1L gene were found, and we described a patient with GRACILE syndrome.

The research broadened the BCS1L gene mutational spectrum linked to GRACILE syndrome, aiding in genetic diagnostics.

Reference: onlinelibrary.wiley.com/doi/10.1111/nep.14086