Paternal gender specificity and mild phenotypes in Charcot–Marie–Tooth type 1A patients with de novo 17p12 rearrangements

Background Charcot–Marie–Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are developed by duplication and deletion of the 17p12 (PMP22) region, respectively. Methods De novo rates were determined in 211 CMT1A or HNPP trio families, and then, analyzed...

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Published in:	Molecular genetics & genomic medicine Vol. 8; no. 9; pp. e1380 - n/a
Main Authors:	Lee, Ah J., Nam, Da E., Choi, Yu J., Noh, Seung W., Nam, Soo H., Lee, Hye J., Kim, Seung J., Song, Gyun J., Choi, Byung‐Ok, Chung, Ki W.
Format:	Journal Article
Language:	English
Published:	Bognor Regis John Wiley & Sons, Inc 01-09-2020 John Wiley and Sons Inc Wiley
Subjects:	Age Charcot-Marie-Tooth disease Charcot–Marie–Tooth disease 1A (CMT1A) Chromatids de novo mutation Drug dosages Gender gender specificity Haplotypes hereditary neuropathy with liability to pressure palsies (HNPP) Liability Mutation Neuropathy Original Parents & parenting Patients Peripheral myelin protein 22 Peripheral neuropathy Phenotypes Signs and symptoms Sister chromatids Statistical analysis Palau
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Summary:	Background Charcot–Marie–Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are developed by duplication and deletion of the 17p12 (PMP22) region, respectively. Methods De novo rates were determined in 211 CMT1A or HNPP trio families, and then, analyzed gender‐specific genetic features and clinical phenotypes of the de novo cases. Results This study identified 40 de novo cases (19.0%). Paternal origin was highly frequent compared to maternal origin (p = .005). Most de novo CMT1A rearrangements occurred between non‐sister chromatids (p = .003), but it was interesting that three of the four sister chromatids exchange cases were observed in the less frequent maternal origin. Paternal ages at the affected child births were slightly higher in the de novo CMT1A group than in the non‐de novo CMT1A control group (p = .0004). For the disability score of CMTNS, the de novo CMT1A group had a slightly lower value compared to the control group (p = .005). Electrophysiological studies showed no significant differences between the two groups. Conclusion This study suggests that de novo CMT1A patients tend to have milder symptoms and that the paternal ages at child births in the de novo group are higher than those of the non‐de novo group. This study identified 40 de novo cases in 211 CMT1A or HNPP trio families. Paternal ages at the affected child births were slightly higher in the de novo CMT1A group than in the non‐de novo CMT1A control group. For the disability score of CMTNS, the de novo CMT1A group had a slightly lower value compared to the control group. This will be the first study to suggest that de novo CMT1A patients tend to have milder symptoms and that the paternal ages at child births in the de novo group are higher than those of the non‐de novo group.
Bibliography:	Funding information This work was supported by Grants of the National Research Foundation (2016R1D1A1B01009186, 2017R1A2B2004699, 2018R1A4A1024506, and 2019R1A2C1087547), and grants of the Korean Health Technology R&D Project, Ministry of Health & Welfare (HI14C3484, and HI16C0426), Republic of Korea. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2324-9269 2324-9269
DOI:	10.1002/mgg3.1380