A novel p.Leu699Pro mutation in MFN2 gene causes Charcot-Marie-Tooth disease type 2A

Sa-Yoon Kang; Keun Hyuk Ko; Jung-Hwan Oh

doi:10.14253/acn.2019.21.1.57

Journal List > Ann Clin Neurophysiol > v.21(1) > 1121233

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Kang, Ko, and Oh: A novel p.Leu699Pro mutation in MFN2 gene causes Charcot-Marie-Tooth disease type 2A

Case Report

Ann Clin Neurophysiol 2019;21(1):57-60.

Published online: 20 January 2019

DOI: https://doi.org/10.14253/acn.2019.21.1.57

A novel p.Leu699Pro mutation in MFN2 gene causes Charcot-Marie-Tooth disease type 2A

Sa-Yoon Kang, Keun Hyuk Ko, Jung-Hwan Oh

Department of Neurology, Jeju National University School of Medicine, Jeju, Korea

Correspondence to Sa-Yoon Kang Department of Neurology, Jeju National University School of Medicine, 102 Jejudae-hak-ro, Jeju 63243, Korea Tel: +82-64-754-8175 Fax: +82-64-717–1630 E-mail: neurokang@jejunu.ac.kr

Received 14 June 2018 Revised 30 November 2018 Accepted 5 December 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Axonal Charcot-Marie-Tooth disease (CMT2) has most frequently been associated with mu-tations in the MFN2 gene. MFN2 encodes mitofusin 2, which is a mitochondrial fusion protein that plays an essential role in mitochondrial function. We report CMT2 in a Korean father and his son that manifested with gait difficulties and progressive atrophy of the lower legs. Molec-ular analysis revealed a novel heterozygous c.2096T>C (p.Leu699Pro) mutation in the exon 18 of MFN2 in both subjects. We suggest that this novel mutation in MFN2 is probably a patho-genic mutation for CMT2.

Keywords: Charcot-Marie-Tooth disease, MFN2, Mutation, Phenotype

References

1. Verhoeven K, Claeys KG, Züchner S, Schröder JM, Weis J, Ceuterick C, et al. MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. Brain. 2006; 129(Pt 8):2093–2102.

2. Cartoni R, Martinou JC. Role of mitofusin 2 mutations in the physiopathology of Charcot-Marie-Tooth disease type 2A. Exp Neurol. 2009; 218:268–273.

3. Stuppia G, Rizzo F, Riboldi G, Del Bo R, Nizzardo M, Simone C, et al. MFN2-related neuropathies: clinical features, molecular pathogenesis and therapeutic perspectives. J Neurol Sci. 2015; 356:7–18.

4. Chung KW, Kim SB, Park KD, Choi KG, Lee JH, Eun HW, et al. Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations. Brain. 2006; 129(Pt 8):2103–2118.

5. Züchner S, De Jonghe P, Jordanova A, Claeys KG, Guergueltcheva V, Cherninkova S, et al. Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2. Ann Neurol. 2006; 59:276–281.

6. Brockmann K, Dreha-Kulaczewski S, Dechent P, Bönnemann C, Helms G, Kyllerman M, et al. Cerebral involvement in axonal Char-cot-Marie-Tooth neuropathy caused by mitofusin 2 mutations. J Neurol. 2008; 255:1049–1058.

7. Del Bo R, Moggio M, Rango M, Bonato S, D'Angelo MG, Ghezzi S, et al. Mutated mitofusin 2 presents with intrafamilial variability and brain mitochondrial dysfunction. Neurology. 2008; 71:1959–1966.

8. Ajroud-Driss S, Fecto F, Ajroud K, Yang Y, Donkervoort S, Siddique N, et al. A novel de novo MFN2 mutation causing CMT2A with upper motor neuron signs. Neurogenetics. 2009; 10:359–361.

9. Züchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, et al. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet. 2004; 36:449–451.

10. Baloh RH, Schmidt RE, Pestronk A, Milbrandt J. Altered axonal mitochondrial transport in the pathogenesis of Charcot-Marie-Tooth disease from mitofusin 2 mutations. J Neurosci. 2007; 27:422–430.

Fig. 1.

(A) Molecular genetic analysis obtained from the sequencing of exon 18 of MFN2 show a heterozygous c.2096T>C (p.Leu699Pro) mutation in the proband and his father. (B) Magnetic resonance imaging of the lower extremities in the proband shows widespread fatty degeneration in most muscles of lower leg except posterior tibial muscle.

Table 1.

The results of nerve conduction studies in proband and his father

Motor NCS	Proband		Father
Motor NCS	Amplitude (mV)	NCV (m/sec)	Amplitude (mV)	NCV (m/sec)
Median (R/L)
TL (ms)		3.2/3.2 (3.6)		3.7/3.4
F-W	15.3/13.9 (5)		17.9/16.8
W-E	14.0/13.5	56/58 (49.9)	17.2/15.9	57/59
E-A	14.0/13.1	67/67 (55.9)	14.3/14.6	69/67
Ulnar (R/L)
TL (ms)		2.3/2.4 (2.5)		2.3/2.3
F-W	13.7/16.3 (5)		20.1/19.8
W-BE	12.9/15.0	60/54 (50.6)	19.9/19.1	56/57
BE-AE	12.7/14.7	53/46 (42.8)	19.5/18.4	60/59
E-A	12.1/13.6	64/67 (52.6)	17.2/17.6	69/65
Peroneal (R/L)
TL (ms)		–/- (4.7)		5.9/5.7
Ankle	NP/NP		0.9/1.1
Knee	NP/NP	–/- (41.8)	0.9/0.8	39/40
Tibial (R/L)
TL (ms)		–/- (5.1)		–/-
Ankle	NP/NP		NP/NP
PF	NP/NP	–/- (40)	NP/NP	–/-
Sensory NCS	Amplitude (μV)	NCV (m/sec)	Amplitude (μV)	NCV (m/sec)
Median (R/L)
F-W	5.0/5.8 (10)	41/38 (41)	4.3/6.1	44/46
W-E	6.0/6.8	55/56 (49)	5.3/5.9	52/48
E-A	64.7/17.6	63/63 (53)	29.2/31.6	58/57
Ulnar (R/L)
F-W	4.7/NP (10)	38/- (39)	3.4/4.8	41/43
W-E	9.0/8.1	56/51 (47)	15.3/13.6	53/51
E-A	25.1/27.6	67/59 (48)	23.2/26.5	56/59
Sural (R/L)	NP/NP (6)	–/- (34)	NP/NP	–/-

NCS, nerve conduction study; NCV, nerve conduction velocity; R/L, right/left; TL, terminal latency; F-W, finger-wrist; W-E, wrist-elbow; E-A, el-bow-axilla; W-BE, wrist-below elbow; BE-AE, below elbow-above elbow; NP, no potentials; PF, popliteal fossa.

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