Similar to other types of pontocerebellar hypoplasias (PCH), subtypes PCH2 (OMIM 277470) and PCH4 (OMIM 225753) are characterized by small cerebellum and brainstem, variable neocortical atrophy, and abnormal mental and motor development. In addition, patients with PCH2 exhibit progressive microcephaly from birth, extrapyramidal dyskinesia, chorea, and epilepsy. PCH4, also known as fatal infantile olivopontocerebellar hypoplasia, is associated with a more severe course and an earlier lethality than PCH2. Mutations in TSEN54 [OMIM 608755], encoding one of the noncatalytic subunits of the tRNA-splicing endonuclease complex, have recently been implicated in the etiology of PCH2A and PCH4. Budde et al (2008) sequenced the TSEN54 gene in 58 patients from the Netherlands and other European countries, Brazil, and Israel. 3/3 patients with PCH4 had mutations detected in TSEN54, and 47/52 patients with PCH2 were homozygous for the p.A307S mutation. Of these 47 patients, 31 shared European ancestry and a haplotype on which p.A307S arose as a founder mutation. Deletions and/or duplications involving the TSEN54 gene as causative of pontocerebellar hypoplasia have been reported.
Specimen Types Accepted
If sending saliva, 2 kits are required.