Three sib-pairs of autopsy-confirmed progressive supranuclear palsy

To describe the clinical, pathological, and genetic features of three sib-pairs of pathologically-confirmed progressive supranuclear palsy (PSP).

We searched the Mayo Clinic neurodegenerative diseases brain bank for cases of PSP in which more than one family member had pathologically-confirmed PSP. Clinical and pathological data were reviewed and all individuals were screened for mutations in MAPT, by sequencing exons 1, 7, and 9-13.

We identified three sib-pairs of pathologically-confirmed PSP. Sufficient information was available to suggest an autosomal dominant inheritance in two. The mean age at symptom onset was 41 years in one pair, and 76 years in the other two. The young onset pair had a p.S285R mutation in MAPT, but no mutations were detected in the other two.

All sib-pairs had typical pathological features of PSP; however, the age at onset of the sib-pair with MAPT mutation was significantly younger than sporadic PSP. Future studies are warranted to identify a possible genetic basis for PSP associated with late onset and typical PSP pathology.