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From HDLS to BANDDOS: fast-expanding phenotypic spectrum of disorders caused by mutations in CSF1R

Journal of Human Genetics volume 66, pages 1139–1144 (2021)Cite this article

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Abstract

Colony-stimulating factor 1 receptor (CSF1R) plays key roles in the development and function of the cells in the monocyte/macrophage lineage, including microglia and osteoclasts. It is well known that mono-allelic mutations of CSF1R cause hereditary diffuse leukoencephalopathy with spheroids (HDLS, OMIM # 221820), an adult-onset progressive neurodegenerative disorder. Recently, a more severe phenotypic spectrum has been identified in individuals with bi-allelic mutations of CSF1R. In addition to leukoencephalopathy of earlier onset than HDLS, the new disease shows brain malformations and skeletal dysplasia compatible with dysosteosclerosis (DOS), thus named “brain abnormalities, neurodegeneration, and dysosteosclerosis” (BANDDOS, OMIM # 618476). In addition, some individuals with bi-allelic missense mutations of CSF1R have been found to present with incomplete BANDDOS where skeletal dysplasia is absent. In this review, we summarize the monogenic disorders caused by mutations in CSF1R and their mutational spectra, and propose a dose-dependent model to explain the complex genotype–phenotype association.

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Acknowledgements

We thank Mrs. Tomoko Kusadokoro for her help in a series of our studies.

Funding

This study is supported by grants from the Japan Society for the Promotion of Science (SI, No. 18H02932) and the Japan Agency For Medical Research and Development (SI, No. 20bm0804006h0104 and 20ek0109486h0001).

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  1. Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan

    Long Guo & Shiro Ikegawa

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  1. Long Guo
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Correspondence to Long Guo.

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Guo, L., Ikegawa, S. From HDLS to BANDDOS: fast-expanding phenotypic spectrum of disorders caused by mutations in CSF1R. J Hum Genet 66, 1139–1144 (2021). https://doi.org/10.1038/s10038-021-00942-w

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