Abstract
Intellectual developmental disorder, X-linked 104 (XLID104), caused by the FRMPD4 gene variant, is a rare X-linked genetic disease that primarily manifests as intellectual disability (ID) and language delay, and may be accompanied by behavioural abnormalities. Currently, only 11 patients from four families have been reported to carry FRMPD4 gene variants. Here, we report a rare case of a Chinese patient with XLID104 who was presented with severe ID and language impairment. Genetic testing results showed that the patient had a novel hemizygous variant on FRMPD4 inherited from the heterozygous variant NM_001368397: c.1772A>C (p.Glu591Ala) carried by his mother. To our knowledge, this variant has not been reported previously. Western blot results for the recombinant plasmid constructed in vitro indicated that the expression of the mutant protein may be reduced. Using molecular dynamics simulations, we predicted that the mutant protein may affect the interaction of the FRMPD4 protein with DLG4. In this study, we expand the spectrum of FRMPD4 variants and suggest that the clinical awareness of the genetic diagnosis of nonsyndromic ID should be strengthened.
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Our team would like to thank the patient and his parents for their participation in the study.
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HP participated in sample/data collection and molecular experiments, reviewed the literature, and drafted the manuscript. HP and FZ contributed to the conception and design of the study, bioinformatics analysis, and figure design. FZ, KC, YZ, WW participated in WES data analysis and reviewed the manuscript. HP and YZ contributed extensively to the interpretation of data. HP, KC, WW were involved in molecular experiments. HP supervised the project, reviewed and revised the manuscript, and approved the final manuscript as submitted. All authors read and approved the final manuscript.
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Corresponding editor: Ashwin Dalal
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Pan, H., Zhu, F., Chen, K. et al. Genetic analysis of a child with severe intellectual disability caused by a novel variant in the FERM domain of the FRMPD4 protein. J Genet 103, 14 (2024). https://doi.org/10.1007/s12041-024-01465-x
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DOI: https://doi.org/10.1007/s12041-024-01465-x