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Identification of a 5 bp duplicate in the AP1S2 gene of an individual with X-linked intellectual disability

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Abstract

Adaptor-related protein complex 1 subunit sigma 2 (AP1S2) is a subunit of AP1 that is crucial for the reformation of the synaptic vesicle. Variants in AP1S2 have been reported to cause a rare neurodevelopmental disorder, Pettigrew syndrome (PGS) (OMIM: 304,340), which is characterized by walking delay, abnormal speech, mild to profound X-linked intellectual disability (XLID), and abnormal brain, and behaviors. Here, we describe a 2-year- and 5-month-old male patient who presented with global developmental delay (GDD). Trio whole exome sequencing (WES) revealed a 5 bp duplicate in the AP1S2 gene (NM_003916.5: exon 2: c.96_100dup, p. Leu34Glnfs*8) predicted to cause early termination of translation, which was inherited from the unaffected mother. The clinical features of our patient were consistent with previous reports. This is the second case in the Chinese family and the eleventh variant found in AP1S2-related XLID. Our findings expand the AP1S2 variant spectrum in neurodevelopmental disorders and provide evidence for the application of WES in PGS diagnosis.

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Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We wish to gratefully thank the patient’s parents for allowing us to publish this clinical report. And also thank Cipher Gene for their sequencing knowledge support. This work was supported by Joint Open Research Fund of Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center (KFKT2021102), the Henan Medical Science and Technique Foundation (212102310221, LHGJ20190337), and the national Health Commission Key Laboratory of Birth Defects Prevention and Henan Key Laboratory of Population Defects Prevention (2021-03).

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Authors and Affiliations

  1. Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, 450052, China

    Dengna Zhu, Mingmei Wang, Yiran Xu & Jiamei Zhang

  2. Commission Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Zhengzhou, 450052, China

    Yiran Xu

  3. Cipher Gene LLC, Beijing, 100080, China

    Fan Yang & Zuozhen Yang

Authors
  1. Dengna Zhu
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  2. Mingmei Wang
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  3. Yiran Xu
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  4. Jiamei Zhang
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  5. Fan Yang
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  6. Zuozhen Yang
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Contributions

DZ and MW conceived and designed the experiments. YX and JZ did the patient recruitment and clinical analysis. FY and ZY did the WES and molecular analysis. DZ wrote the first draft of the manuscript. All authors reviewed and approved the final manuscript.

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Correspondence to Dengna Zhu.

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Supplementary Fig. 1

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10048_2022_691_MOESM1_ESM.tif

High Resolution Image MRI results. (a). A high single of T2 FLAIR was noted. (b). DWI was normal with no diffusion limitation. The short corpus callosum is shown in (c). No obvious abnormality was shown in the repeat MRI examination (d-f).Abbreviations: DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery. (TIF 6945 KB)

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Zhu, D., Wang, M., Xu, Y. et al. Identification of a 5 bp duplicate in the AP1S2 gene of an individual with X-linked intellectual disability. Neurogenetics 23, 179–185 (2022). https://doi.org/10.1007/s10048-022-00691-8

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  • DOI: https://doi.org/10.1007/s10048-022-00691-8

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