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Case Reports
. 2015 Feb;21(2):101-5.
doi: 10.1016/j.parkreldis.2014.10.028. Epub 2014 Nov 15.

Three sib-pairs of autopsy-confirmed progressive supranuclear palsy

Shinsuke Fujioka  1 , Monica Y Sanchez Contreras  2 , Audrey J Strongosky  3 , Kotaro Ogaki  2 , Nathaniel Robb Whaley  4 , Pawel M Tacik  3 , Jay A van Gerpen  3 , Ryan J Uitti  3 , Owen A Ross  2 , Zbigniew K Wszolek  5 , Rosa Rademakers  2 , Dennis W Dickson  6
Affiliations
Case Reports

Three sib-pairs of autopsy-confirmed progressive supranuclear palsy

Shinsuke Fujioka et al. Parkinsonism Relat Disord. 2015 Feb.

Abstract

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

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: MAPT; Progressive supranuclear palsy; p.S285R; tau pathology.

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Figures

Figure 1
Figure 1. Pedigrees of three sib-pairs of progressive supranuclear palsy (A), and pathological features of Case 2 (B–K)
Standard pedigree symbols were used. Round symbols indicate females; squares indicate males; and diagonal lines indicate that the individual is deceased. Diamonds were used to disguise gender. +/− indicates heterozygous S285R mutation genotype. Numbers within the diamonds indicate the number of siblings. The solid arrowhead indicates the proband. * indicates autopsy patients. Macroscopic features of the left hemibrain (B), severe atrophy of subthalamic nucleus (arrow) (C), midbrain atrophy and substantia nigra pigment loss (arrow) (D), and superior cerebellar peduncle atrophy (arrow) (E). H&E staining shows severe neuronal loss and gliosis in the subthalamic nucleus (F) and substantia nigra (G). Tau immunohistochemistry reveal typical tau pathology in the motor cortex (H), striatum (I), subthalamic nucleus (J), and substantia nigra (K).
See this image and copyright information in PMC

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