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A commentary on “Recurrence mutation in RBBP8 gene causing non-syndromic autosomal recessive primary microcephaly; geometric simulation approach for insight into predicted computational models”

Journal of Human Genetics volume 68, pages 793–794 (2023)Cite this article

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I read the recently published article “Recurrence mutation in RBBP8 gene causing non-syndromic autosomal recessive primary microcephaly; geometric simulation approach for insight into predicted computational models” by Batool et al. [1], with great interest. The article reported a biallelic sequence variant (c.1807_1808delAT) in the RBBP8 gene which reportedly to be the cause of a non-syndromic primary microcephaly family. This sequence variant leads to a frameshift mutation which further produced a premature termination codon (PTC). To illustrate the contribution of the mutation to the non-syndromic autosomal recessive primary microcephaly, the authors used PROVEAN software to predict the deleterious effect of the variation on protein and stated the possibility that the variant leads to non-sense mediated mRNA decay (NMD) accordingly (in the DISCUSSION section).

However, PROVEAN is not designed to analyze the frameshift mutation, but to predict the pathogenic effect of variations including single or multiple amino acid (AA) substitutions, and in-frame insertions or deletions [2]. Briefly, the program predicts the functional impact of a variation through homologous protein alignment and then calculates a delta alignment score based on the alignment to measure the damaging effect of the variation.

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References

  1. Batool T, Irshad S, Riaz M, Mahmood Baig S, Nuernberg P, Hussain MS. Recurrence mutation in RBBP8 gene causing non-syndromic autosomal recessive primary microcephaly; geometric simulation approach for insight into predicted computational models. J Hum Genet. 2023. https://doi.org/10.1038/s41588-019-0517-5.

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  1. Department of Bioinformatics, 01life Institute, Shenzhen, 518000, Guangdong, China

    Jiajie Pu

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Correspondence to Jiajie Pu.

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Pu, J. A commentary on “Recurrence mutation in RBBP8 gene causing non-syndromic autosomal recessive primary microcephaly; geometric simulation approach for insight into predicted computational models”. J Hum Genet 68, 793–794 (2023). https://doi.org/10.1038/s10038-023-01165-x

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