Prolyl endopeptidase-like (PREPL) deficiency (MIM# 616224) is a rare autosomal recessive inherited congenital myasthenic syndrome characterized by neonatal hypotonia, feeding problems, mild dysmorphism, and neuromuscular symptoms, followed by hyperphagia and obesity in later childhood. Some patients also exhibit growth deficits, sexual hormone deficiency, and cognitive impairments. This syndrome is caused by biallelic mutations in PREPL. To date, only one nucleotide deletion and seven small microdeletions in PREPL have been reported. Here we report a female patient with a novel homozygous frameshift mutation in PREPL (NM_006036.4, c.342delA:p.Val115Leufs*39). Her clinical features are similar to those of previously reported cases. The mutation is the first homozygous point mutation reported in humans.
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We thank the patient’s family for their cooperation in this study. We also thank Mr. Esteban Barnafi for his help in collecting and sending samples. We thank Barry Patel, Ph.D., from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
This work was supported by grants from Research on Measures for Intractable Diseases; Comprehensive Research on Disability Health and Welfare; the Strategic Research Program for Brain Science; Initiative on Rare and Undiagnosed Diseases in Pediatrics and Initiative on Rare and Undiagnosed Diseases for Adults from the Japan Agency for Medical Research and Development; Grants-in-Aid for Scientific Research (A and B) from the Japan Society for the Promotion of Science; Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems from the Japan Science and Technology Agency; grants from the Ministry of Health, Labour and Welfare; the Takeda Science Foundation; the Yokohama Foundation for Advancement of Medical Science; and the Hayashi Memorial Foundation for Female Natural Scientists.
Conflict of interest
The authors declare that they have no conflict of interest.
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Silva, S., Miyake, N., Tapia, C. et al. The second point mutation in PREPL: a case report and literature review. J Hum Genet 63, 677–681 (2018). https://doi.org/10.1038/s10038-018-0426-y