Title: Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese
patients with Wilson disease
Version: 4 Date: 23 Jan 2021
Reviewer's report:
This is very interesting paper describing the genetic examination of large cohort of WD patients,
the authors described the frequency of different mutation, finding also new pathogenic variants.
and discussing the genotype-phenotype correlations I have a comment to the discussion section:
1) there are several papers describing the genetic studies in WD in different populations
(European, Korean, Irania, etc...) published, describing also significance of different mutations
quite recently, could you discuss them  e.g. Kluska, et al Whole-exome sequencing identifies
novel pathogenic variants across the ATP7B gene and some modifiers of Wilson's disease
phenotype. Liver Int 2019,   or reviews chapters describing genetic and epidemiology in
Handbook of Clinical Neurology 2017..  There are also several papers describing the effect of
different mutation in ATP7B
2) discussing genotype-phenotype correlation there are also several papers describing the effect
of type of mutation (frameshift, etc) on copper metabolism as well as phenotype presentation -
could You compare Your results with literature?
4) finally almost 20% patients were not confirmed genetically, how could You explain it? could
You compare it with data from other studies?
5) ten bibiliography should be updated on papers published in two-three years (several genetic
as well as epigenetic  studies were performed in WD as well as quite new review papers),
I recommend to accept this interesting paper after revision
Title: Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese
patients with Wilson disease
Version: 4 Date: 23 Jan 2021
Reviewer's report:
This is very interesting paper describing the genetic examination of large cohort of WD patients,
the authors described the frequency of different mutation, finding also new pathogenic variants.
and discussing the genotype-phenotype correlations I have a comment to the discussion section:
1) there are several papers describing the genetic studies in WD in different populations
(European, Korean, Irania, etc...) published, describing also significance of different mutations
quite recently, could you discuss them  e.g. Kluska, et al Whole-exome sequencing identifies
novel pathogenic variants across the ATP7B gene and some modifiers of Wilson's disease
phenotype. Liver Int 2019,   or reviews chapters describing genetic and epidemiology in
Handbook of Clinical Neurology 2017..  There are also several papers describing the effect of
different mutation in ATP7B
2) discussing genotype-phenotype correlation there are also several papers describing the effect
of type of mutation (frameshift, etc) on copper metabolism as well as phenotype presentation -
could You compare Your results with literature?
4) finally almost 20% patients were not confirmed genetically, how could You explain it? could
You compare it with data from other studies?
5) ten bibiliography should be updated on papers published in two-three years (several genetic
as well as epigenetic  studies were performed in WD as well as quite new review papers),
I recommend to accept this interesting paper after revision
Please review this paper.
user
Title: Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese
patients with Wilson disease
Version: 4 Date: 23 Jan 2021
Reviewer's report:
This is very interesting paper describing the genetic examination of large cohort of WD patients,
the authors described the frequency of different mutation, finding also new pathogenic variants.
and discussing the genotype-phenotype correlations I have a comment to the discussion section:
1) there are several papers describing the genetic studies in WD in different populations
(European, Korean, Irania, etc...) published, describing also significance of different mutations
quite recently, could you discuss them  e.g. Kluska, et al Whole-exome sequencing identifies
novel pathogenic variants across the ATP7B gene and some modifiers of Wilson's disease
phenotype. Liver Int 2019,   or reviews chapters describing genetic and epidemiology in
Handbook of Clinical Neurology 2017..  There are also several papers describing the effect of
different mutation in ATP7B
2) discussing genotype-phenotype correlation there are also several papers describing the effect
of type of mutation (frameshift, etc) on copper metabolism as well as phenotype presentation -
could You compare Your results with literature?
4) finally almost 20% patients were not confirmed genetically, how could You explain it? could
You compare it with data from other studies?
5) ten bibiliography should be updated on papers published in two-three years (several genetic
as well as epigenetic  studies were performed in WD as well as quite new review papers),
I recommend to accept this interesting paper after revision
assistant