VPS53 mutations cause progressive cerebello-cerebral atrophy type 2 (PCCA2)

Miora Feinstein, Hagit Flusser, Lerman Sagie Tally, Bruria Ben-Zeev, Dorit Lev, Orly Agamy, Idan Cohen, Rotem Kadir, Sara Sivan, Esther Leshinsky-Silver, Barak Markus, Ohad S. Birk

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Background: Progressive cerebello-cerebral atrophy (PCCA) leading to profound mental retardation, progressive microcephaly, spasticity and early onset epilepsy, was diagnosed in four non-consanguineous apparently unrelated families of Jewish Moroccan ancestry. Common founder mutation(s) were assumed. Methods: Genome-wide linkage analysis and whole exome sequencing were done, followed by realtime PCR and immunofluorescent microscopy. Results: Genome-wide linkage analysis mapped the disease-associated gene to 0.5 Mb on chromosome 17p13.3. Whole exome sequencing identified only two mutations within this locus, which were common to the affected individuals: compound heterozygous mutations in VPS53, segregating as expected for autosomal recessive heredity within all four families, and common in Moroccan Jews (~1:37 carrier rate). The Golgiassociated retrograde protein (GARP) complex is involved in the retrograde pathway recycling endocytic vesicles to Golgi; c.2084A>G and c.1556+5G>A VPS53 founder mutations are predicted to affect the C-terminal domain of VPS53, known to be critical to its role as part of this complex. Immunofluorescent microscopy demonstrated swollen and abnormally numerous CD63 positive vesicular bodies, likely intermediate recycling/late endosomes, in fibroblasts of affected individuals. Conclusions: Autosomal recessive PCCA type 2 is caused by VPS53 mutations.

Original languageEnglish
Pages (from-to)303-308
Number of pages6
JournalJournal of Medical Genetics
Issue number5
StatePublished - 2014
Externally publishedYes


Dive into the research topics of 'VPS53 mutations cause progressive cerebello-cerebral atrophy type 2 (PCCA2)'. Together they form a unique fingerprint.

Cite this