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Postzygotic inactivating mutation of KIF13A located at chromosome 6p22.3 in a patient with a novel mosaic neuroectodermal syndrome

Journal of Human Genetics volume 66, pages 825–829 (2021)Cite this article

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Abstract

Hypomelanosis of Ito (HMI) is part of a neuroectodermal syndrome characterized by distinctive skin manifestations with or without multisystemic involvements. In our undiagnosed diseases program, we have encountered a 3-year-old girl presenting with characteristic skin hypopigmentation suggesting HMI and developmental delay. An exome and genome approach utilizing next-generation sequencing revealed a heterozygous de novo frameshift variant in the KIF13A gene, i.e., NM_022113.6: c.2357dupA, resulting in nonsense-mediated decay. The low mutant allelic ratio suggested that the mutation has occurred postzygotically leading to embryonic mosaicism. Functionally, K1F3A regulates cell membrane blebbing and migration of neural crest cells by controlling recycling of RHOB to the plasma membrane and is also involved in melanosome biogenesis. Importantly, hypopigmentation of the skin has been reported in chr 6p22.3-p23 microdeletion syndrome supporting the association of KIF13A haploinsufficiency with the novel neuroectodermal syndrome. With the increased availability of genome sequencing, we envisage more genetic causes of HMI will be identified in the future.

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Author notes

  1. These authors contributed equally: Ching-Wan Lam, Candace Yim Chan

Authors and Affiliations

  1. Department of Pathology, The University of Hong Kong, Hong Kong, China

    Ching-Wan Lam & Sharon Tzu-Lun Chang

  2. Department of Pathology, Princess Margaret Hospital, Hong Kong, China

    Candace Yim Chan

  3. Department of Pathology, Queen Mary Hospital, Hong Kong, China

    Candace Yim Chan & Ka-Chung Wong

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  1. Ching-Wan Lam
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  2. Candace Yim Chan
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  3. Ka-Chung Wong
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  4. Sharon Tzu-Lun Chang
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Correspondence to Ching-Wan Lam.

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Lam, CW., Chan, C.Y., Wong, KC. et al. Postzygotic inactivating mutation of KIF13A located at chromosome 6p22.3 in a patient with a novel mosaic neuroectodermal syndrome. J Hum Genet 66, 825–829 (2021). https://doi.org/10.1038/s10038-020-00883-w

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