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Int. J. Mol. Sci. 2017, 18(4), 770; doi:10.3390/ijms18040770

Rapid Identification of Pathogenic Variants in Two Cases of Charcot-Marie-Tooth Disease by Gene-Panel Sequencing

1
Department of Clinical Pathology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China
2
Department of Paediatrics & Adolescent Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China
3
Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China
4
Centre for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Stephen A. Bustin
Received: 24 February 2017 / Revised: 28 March 2017 / Accepted: 31 March 2017 / Published: 5 April 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Charcot-Marie-Tooth disease (CMT) is a common inherited peripheral neuropathy affecting up to 1 in 1214 of the general population with more than 60 nuclear genes implicated in its pathogenesis. Traditional molecular diagnostic pathways based on relative prevalence and clinical phenotyping are limited by long turnaround time, population-specific prevalence of causative variants and inability to assess multiple co-existing variants. In this study, a CMT gene panel comprising 27 genes was used to uncover the pathogenic mutations in two index patients. The first patient is a 15-year-old boy, born of consanguineous parents, who has had frequent trips and falls since infancy, and was later found to have inverted champagne bottle appearance of bilateral legs and foot drop. His elder sister is similarly affected. The second patient is a 37-year-old woman referred for pre-pregnancy genetic diagnosis. During early adulthood, she developed progressive lower limb weakness, difficulties in tip-toe walking and thinning of calf muscles. Both patients are clinically compatible with CMT, have undergone multiple genetic testings and have not previously received a definitive genetic diagnosis. Patients 1 and 2 were found to have pathogenic homozygous HSPB1:NM_001540:c.250G>A (p.G84R) variant and heterozygous GDAP1:NM_018972:c.358C>T (p.R120W) variant, respectively. Advantages and limitations of the current approach are discussed. View Full-Text
Keywords: Charcot-Marie-Tooth disease (CMT); hereditary motor and sensory neuropathy (HMSN); pathogenic variants; gene panel; next-generation sequencing (NGS) Charcot-Marie-Tooth disease (CMT); hereditary motor and sensory neuropathy (HMSN); pathogenic variants; gene panel; next-generation sequencing (NGS)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Ho, C.-C.; Tai, S.-M.; Lee, E.C.-N.; Mak, T.S.-H.; Liu, T.K.-T.; Tang, V.W.-L.; Poon, W.-T. Rapid Identification of Pathogenic Variants in Two Cases of Charcot-Marie-Tooth Disease by Gene-Panel Sequencing. Int. J. Mol. Sci. 2017, 18, 770.

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