Abstract
Börjeson-Forssman-Lehman Syndrome (BFLS) is a rare X-linked recessive syndrome characterized by intellectual disability, developmental delay, obesity, epilepsy, swelling of the subcutaneous tissues of the face, large but not deformed ears, hypogonadism, and gynecomastia. Pathogenic mutations in PHD finger protein 6 (PHF6) have been reported to cause BFLS. In this study, we describe two male siblings with mild intellectual disability, global developmental delay, short stature, microcephaly, and nyctalopia. Whole exome sequencing of the affected siblings and the parents identified a missense variant (c.413C > G) in the PHF6 gene, which leads to alteration of a serine residue at position 138 to cysteine. This mutation is located in a highly conserved region. Sanger sequencing confirmed the segregation of this mutation in the family in an X-linked recessive fashion. Multiple mass spectrometry-based proteomic studies have reported phosphorylation at serine 138 that describes the possible role of serine 138 in signaling. This novel variant in PHF6 gene helped in establishing a diagnosis of BFLS.
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Acknowledgments
We thank the patients and family members for participating in this study.
Funding
This work was funded under the DBT-BioCARe scheme by Department of Biotechnology (DBT), Government of India (BT/PR18182/BIC/101/937/2016). This work was supported by the Wellcome Trust/DBT India Alliance Margdarshi Fellowship (grant number IA/M/15/1/502023) awarded to Akhilesh Pandey. Babylakshmi Muthusamy is a recipient of DBT-BioCARe Women Scientist Award from DBT, Government of India. Aravind K. Bandari is a recipient of Senior Research Fellowship from CSIR, Government of India.
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Conceptualization: Babylakshmi Muthusamy, Akhilesh Pandey, and Satish Chandra Girimaji; Data curation: Babylakshmi Muthusamy and Anikha Bellad; Analysis: Babylakshmi Muthusamy; Funding acquisition: Babylakshmi Muthusamy, Akhilesh Pandey, and Satish Chandra Girimaji; Investigation: Babylakshmi Muthusamy; Methodology: Babylakshmi Muthusamy; Project administration: Babylakshmi Muthusamy, Resources: Babylakshmi Muthusamy, Akhilesh Pandey, and Satish Chandra Girimaji; Software: Babylakshmi Muthusamy; Supervision: Babylakshmi Muthusamy, Akhilesh Pandey, and Satish Chandra Girimaji; Visualization: Babylakshmi Muthusamy; Writing – original draft: Babylakshmi Muthusamy and Anikha Bellad; Writing – review and editing: All authors.
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This study was approved by the institutional ethical committee at National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (include name of committee + reference number) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Appropriate informed consent was obtained from the parents of the patients as the patients were minor. This article does not contain any studies with animals performed by any of the authors.
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Bellad, A., Bandari, A.K., Pandey, A. et al. A Novel Missense Variant in PHF6 Gene Causing Börjeson-Forssman-Lehman Syndrome. J Mol Neurosci 70, 1403–1409 (2020). https://doi.org/10.1007/s12031-020-01560-5
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DOI: https://doi.org/10.1007/s12031-020-01560-5