Title: Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese
patients with Wilson disease
Version: 4 Date: 10 Feb 2021
Reviewer's report:
The authors performed genetic analysis of ATP7B in a series of 103 southern Chinese patients
with clinical diagnosis of Wilson Disease (WD). Next, they tried to correlate their findings
with those previously reported in a selection of WD clinical series from China by means of a
systematic review. I have some observations in order to improve writing. Also, I have found
some issues to be clarified.
-Variants always should be described following HGVS nomenclature recommendations (i.e:
c.2333G>T (p.Arg778Leu)).
-Variant classification as pathogenic, likely pathogenic, benign etc. should rely on ACMG
standard guidelines for interpretation of variants. In silico predictions are included in this criteria,
but solely are insufficient to determine pathogenicity.
-“hotspot” is well written, “hot spot” not.
-Graphics from Figures 3 and 4 are in Chinese, so it was not possible to revise numeric data
properly.
-Concept of “novel” variant should be revised. A variant is considered “novel” the first time that
it is reported in literature. To call as “novel” variants those reported the first time by another
authors seems confusing.
-In this paper, seven variants are reported as novel. However, in four of them there is no novelty
as they have already been identified in different Chinese clinical series of WD in the last five
years:
c.2075T>C (p.Leu692Pro), published by Yuan et al., 2015; Li et al., 2019
c.3209C>G (Pro1070Arg), Dong et al., 2016
c.3677C>T (p.Thr1226Ile), Hua et al., 2016
c.3793G>T (p.Val1265Leu) Poon et al., 2016
-It is not well explained if authors have performed segregation analysis to confirm biallelic
mutations.
-Discussion line 332: Several studies have demonstrated that mutations in ATOX1 and
COMMD1 are not responsible of the WD phenotype.
Title: Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese
patients with Wilson disease
Version: 4 Date: 10 Feb 2021
Reviewer's report:
The authors performed genetic analysis of ATP7B in a series of 103 southern Chinese patients
with clinical diagnosis of Wilson Disease (WD). Next, they tried to correlate their findings
with those previously reported in a selection of WD clinical series from China by means of a
systematic review. I have some observations in order to improve writing. Also, I have found
some issues to be clarified.
-Variants always should be described following HGVS nomenclature recommendations (i.e:
c.2333G>T (p.Arg778Leu)).
-Variant classification as pathogenic, likely pathogenic, benign etc. should rely on ACMG
standard guidelines for interpretation of variants. In silico predictions are included in this criteria,
but solely are insufficient to determine pathogenicity.
-“hotspot” is well written, “hot spot” not.
-Graphics from Figures 3 and 4 are in Chinese, so it was not possible to revise numeric data
properly.
-Concept of “novel” variant should be revised. A variant is considered “novel” the first time that
it is reported in literature. To call as “novel” variants those reported the first time by another
authors seems confusing.
-In this paper, seven variants are reported as novel. However, in four of them there is no novelty
as they have already been identified in different Chinese clinical series of WD in the last five
years:
c.2075T>C (p.Leu692Pro), published by Yuan et al., 2015; Li et al., 2019
c.3209C>G (Pro1070Arg), Dong et al., 2016
c.3677C>T (p.Thr1226Ile), Hua et al., 2016
c.3793G>T (p.Val1265Leu) Poon et al., 2016
-It is not well explained if authors have performed segregation analysis to confirm biallelic
mutations.
-Discussion line 332: Several studies have demonstrated that mutations in ATOX1 and
COMMD1 are not responsible of the WD phenotype.
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: 10 Feb 2021
Reviewer's report:
The authors performed genetic analysis of ATP7B in a series of 103 southern Chinese patients
with clinical diagnosis of Wilson Disease (WD). Next, they tried to correlate their findings
with those previously reported in a selection of WD clinical series from China by means of a
systematic review. I have some observations in order to improve writing. Also, I have found
some issues to be clarified.
-Variants always should be described following HGVS nomenclature recommendations (i.e:
c.2333G>T (p.Arg778Leu)).
-Variant classification as pathogenic, likely pathogenic, benign etc. should rely on ACMG
standard guidelines for interpretation of variants. In silico predictions are included in this criteria,
but solely are insufficient to determine pathogenicity.
-“hotspot” is well written, “hot spot” not.
-Graphics from Figures 3 and 4 are in Chinese, so it was not possible to revise numeric data
properly.
-Concept of “novel” variant should be revised. A variant is considered “novel” the first time that
it is reported in literature. To call as “novel” variants those reported the first time by another
authors seems confusing.
-In this paper, seven variants are reported as novel. However, in four of them there is no novelty
as they have already been identified in different Chinese clinical series of WD in the last five
years:
c.2075T>C (p.Leu692Pro), published by Yuan et al., 2015; Li et al., 2019
c.3209C>G (Pro1070Arg), Dong et al., 2016
c.3677C>T (p.Thr1226Ile), Hua et al., 2016
c.3793G>T (p.Val1265Leu) Poon et al., 2016
-It is not well explained if authors have performed segregation analysis to confirm biallelic
mutations.
-Discussion line 332: Several studies have demonstrated that mutations in ATOX1 and
COMMD1 are not responsible of the WD phenotype.
assistant