Ethics approval and consent to participate
The study was approved from research and ethical committee, International Islamic University, Islamabad, Pakistan, under the case No. IIU (BI & BT) FBAS-2017 and all the experiments were performed after taking the written informed consent of the subjected family and written consents were obtained from the parents or legal guardians of participant under the age of 16.
Consent for publication
We obtained written informed consent for publication of identifying images or other personal or clinical details was obtained from all of the participants. In the case of minors (Individuals younger than the age of 18) consent for publication were obtained from their parents or legal guardians.
Availability of data and material
WES analysis reported submitted in HARVARD dataverse, available online by using following link: https://doi.org/10.7910/DVN/9NP4JV and WES excel file available online by using following link: https://doi.org/10.7910/DVN/ELJ2ZM. The mutation identified in this study is deposited in the ClinVar repository and available online by using accession number: SCV001370544. Protein sequence of the SMS gene obtained from the UniPortKB with accession number: P52788. However additional information is provided in supplementary file. The 3D protein structure model was built by using SWISS-MODEL. Winccot software was used for introducing mutations to structure and Structural effects of a mutation are analyzed through HOPE server. PyMOL was used for representing structural figures. Report can be retrieved from link: https://www3.cmbi.umcn.nl/hope/report/5f089c8bfc0fd33a55c7246d/ .
The authors declare that they have no competing interests.
This work was supported by the National Natural Science Foundation of China grant Numbers (81671268 and 81870844), National key R&D program of China (2017YFC0907501) and Chongqing and Science Technology Bureau (2018MSXM073) for laboratory work; and the Higher Education Commission of Pakistan grant number (7028) for sampling and detailed diagnosis. The funders did not play any role in the study design, data collection, interpretation and preparation of the manuscript.
TJQ, HQ and HMJH designed the research and QW and JY performed the experiments; AA and DL conducted interpretation of data; TJQ, HQ and AM wrote the manuscript and analysed the data; IB arranged and analyzed the clinical date such the X-ray images etc; AM and IB performed in silico analysis. HQ Edited the manuscript and provided practical work funds. Obtaining supervision: HQ, JY, AM, HMJH. HQ and AM contributed equally to this work. All the authors read, revised and approved the final version of the article.
We highly acknowledge participation of both affected and unaffected members of family. We are thankful to Dr Zhu Yijian, Chongqing Population and Family Planning, Science and Technology Research Institute, China, for his valuable comments.