1. Please separate the consent section into statements regarding:
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1 Author s response to reviews Title: Next-generation sequencing for D47N mutation in Cx50 analysis associated with autosomal dominant congenital cataract in a six-generation Chinese family Authors: chao shen (oahcnehs@163.com) Jingbing Wang (wjbzyydq@163.com) Xiaotang Wu (wuxiaotang@yeah.net) Fuchao Wang (xywfc@qq.com) Yang Liu (ly1333@163.com) Xiaoying Guo (xiaoying200471@163.com) Yanfei Cao ( @163.com) Lina Zhang (zhanglina9@126.com) Xiuhua Cao (cxhdq@sohu.com) Hongxing Ma (mahongxing@hotmail.com) Version: 2 Date: 04 Feb 2017 Author s response to reviews: Response to Reviews: Please delineate more clearly over what number of generations you obtained sequencing data from. Please also describe how clinical history was collected for the 6 stated generations. 1. Please separate the consent section into statements regarding: A. Sequencing of participant DNA.
2 - Please clarify whether consent was obtained in written or verbal form for sequencing of participant DNA. - Please also describe the consent process further. - Please note that if study participants are children (under 16 years of age), consent to participate needed to have been collected from the parents/guardians. If there are participants under 16 years of age, please add an additional statement describing consent procedures. Answer: Thank you for your advices. In the process of scientific research or medical treatment, the signing of informed written consent is a basic and routine work, so we don t think there have some problems. To capture and manage informed consents, we typically use paper-based consent forms which are stored in a document handing system after obtaining the necessary signatures. We did some appropriate changes in the paper. In Family data and isolation of genomic DNA section, the sentence Detail family medical history was recorded by interviewing the family members had been inserted and Informed consent was obtained from all participants of the family had been revised as Informed written consent was obtained from all participants of the family. We also inserted the sentence If the participants are children (under 16 years of age), the informed consent was signed by their parents in this section. B. Use of clinical history - Please state how consent was obtained for the use of information from clinical records for all individuals. Please state any permissions required for their access. - Furthermore as we note clinical history spans 6 generations, we request clarification of whether all participants were alive at the time of the study. If any patients are deceased please provide additional information about how consent was obtained for the use of their data in this study.
3 The clinical records were obtained by interviewing the family members. Answer: Thank you for your comments. Consent was obtained directly by interviewing the individuals. Although the clinical history spans 6 generations, the participants just span 4 generations. By the time of the study, all participants were alive. 2. We note significant overlap between this study and a previously published study by the same authors Please clarify the following: I. If these are based on the same study population- this must be explicitly stated and the previously published paper should be referenced within the methodology section. II. If this study is related to the previously published data set ie. An extension of the previous paper (Another evidence for a D47N mutation in GJA8 associated with autosomal dominant congenital cataract Wang 2011) -What does adding an additional 2 generations and using NGS (rather than PCR) add to the literature (compared to previously published paper)? III. Does the current study produce different qualitative or quantitative results compared to the previously published study? Please add this information to the manuscript. Answer: Thank you for your comments. Our study is different from the previously published study which you mentioned above. The six generation autosomal dominant congenital cataract family we conducted originates from the province of Heilong Jiang, China. And the Wang s study population came from the city of Shang Hai, China. Although the two study populations have the same pathogenic gene and pathogenic loci, they do not have any relations. 3. We note that it appears sequencing was only performed on individuals from 4 generations, while clinical history was present for all 6 generations. If this is the case please ensure that this distinction between sequencing and clinical data is made clearer within the manuscript. Answer: Thank you for your comments. Yes, sequencing was performed on individuals from 4 generations and clinical history was present for all 6 generations. Clinical data help us to ensure the inheritance mode of the Chinese cataract pedigree. And sequencing data help us to find the potential pathogenic gene and pathogenic loci. In the methods section, we mentioned that 27
4 family members from 4 generations were recruited in our study, and all participants underwent ophthalmologic examinations. The following paragraph we mentioned we selected 10 patients and 1 unaffected member of the family to sequenced, and the rest 16 participants were taken next-generation sequenced to validate the mutation. We think it is clear that the clinical history data and sequencing data came from different generations. In the result section, we also mentioned the difference between clinical history data and sequencing data. 4. Thank you for providing an authors contributions section. Please note that based on the current authors contributions section, several listed authors (YL and LZ) do not automatically qualify for authorship as provision of materials alone does not usually justify authorship. We ask that you ensure that author contributions are in line with the ICMJE guidelines (below), and that all listed authors have performed all four points specified below. Answer: Thank you for your comments. I apologized for the confusion. Actually, Yang Liu and Lina Zhang also did some statistical work. We are sorry about that misunderstand. We have revised the author contributions. 5. Additionally we note Dianjun Sun is mentioned in the authors contribution section, but not currently listed as an author on the manuscript. Please either: A. Remove reference to contributions of Diajun Sun. B. Fill out and return a Change in Authorship form to officially add them as an author. Answer: Thank you for your comments. I apologized for the mistake. We have remove reference to contributions of Dianjun Sun. 6. Please create a funding subsection as per BMC guidelines. Within this section, all sources of funding for the research reported should be declared. The role of the funding body in the design
5 of the study and collection, analysis, and interpretation of data and in writing the manuscript should be declared. Answer: Thank you for your comments. The funding subsection had been inserted. 7. Please move the list of abbreviations to the end of the manuscript (right before the declarations section). Answer: Thank you for your comments. The list of abbreviations had been moved to the end of the manuscript. 8. Please ensure that when you upload your revised submission that it is in the final form for publication Please remove any tracked changes or highlighting and include only a single clean copy of the manuscript. Answer: Thank you for your comments. The paper had been revised according to the request.
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