Referee 2's review (Budka and Kovacs):

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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication, the manuscript has been revised in light of these comments and to address other editorial requirements.
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This is a well-written and sufficiently documented clincal and genetic description of 4 CJD patients with a mutation in codon 188 (either T88K or T188R) of the prion protein gene. One of the two mutations is new. In one patient a full neuropathological report is given. As such cases are very rare, clinicopathological descriptions are useful, and the present study widens our knowledge about the genetic background of human prion diseases. The Figures and Tables are representative and informative.

There are some minor points that need to be addressed:
1. In the abstract authors should indicate how many cases with T188R and how many with T188K are described.
2. Page 4, paragraph 2, sentence 3: Here reference would be useful.
3. Page 6, paragraph 2: Source of antibody 15G7 should be indicated, like for others.
4. Patient A: was this patient of German or Asian descent?
5. Page 10, Patient A: Authors should indicate what is the normal level of NSE in the CSF in their laboratory. The two unspecific symmetrical lesions in the white matter sound a little bit odd, this should be specified (high or low signal, size, number; infarct, demyelination, artefact etc). According to the authors, VEP was typical for a demyelinating lesion on both sides. This should be specified, in particular the localization (did the VEP indicate a lesion in the optic nerves, chiasma or the visual pathways posterior to the chiasma?).
6. Patient B: Here again: is the NSE level above or below normal? MRI signal in the basal ganglia: was it symmetrical? MRI shows unspecific (high signal or low signal, size, number?) white matter lesions frontoparietal: uni or bilateral? Hypoperfusion of the parietal cortex: did the patient have parietal lobe (or corticobasal) syndrome?
7. Patient C: What is meant by "weak" PSWC? Here also: is the NSE level above or below normal?
8. Page 15, line 10: "A loss of cerebral white matter". Please specifiy: was there fibre loss, demyelination or macrophage activity or only myelin pallor?
9. Page 17, line 5: "were born only around 140 from each other" Perhaps the authors meant to describe the diameter in km of area the patients were within.
10. Page 17, second paragraph: line 6: More recent WHO publications are better suited for citation.