Evidence that autosomal recessive spastic cerebral palsy-1 (CPSQ1) is caused by a missense variant in .

A subset of individuals diagnosed with cerebral palsy will have an underlying genetic diagnosis. Previously, a missense variant in was described as a candidate mutation in a single family diagnosed with autosomal recessive spastic cerebral palsy-1 (CPSQ1; OMIM 603513). Following the ascertainment of a further branch of the CPSQ1 kindred, we found that the previously reported variant did not segregate with the neurological disease phenotype in the recently ascertained branch of the kindred. Following genetic linkage studies to map autozygous regions and whole-exome sequencing, a missense variant (c.527 T > C; p. Leu176Pro, rs773333490) in the gene was detected and found to segregate with disease status in both branches of the kindred. encodes a 371-amino acid protein (4-Hydroxyphenylpyruvate Dioxygenase Like) that localizes to mitochondria but whose function is uncertain. Recently, biallelic loss of function variants and missense substitution-causing variants in were reported to cause a childhood onset progressive spastic movement disorder with a variable presentation. These findings suggest that related neurological disease may mimic spastic cerebral palsy and that should not be included in diagnostic gene panels for inherited cerebral palsy.