A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-tooth disease

BMC Medical Genetics

Byung-Ok Choi¹  Ki Wha Chung⁴  Sung-Chul Jung⁵  Heasoo Koo³  Jeong Hyun Yoo⁶  Bo Ram Yoon⁴  Young Se Hyun⁴  Yu-Ri Choi⁵  Jin-Mo Park²  Ja Hyun Lee⁴  Young Bin Hong¹ 

[1] Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong Gangnam-Gu, Seoul 135-710, Korea;Department of Neurology, School of Medicine, Ewha Womans University, Seoul, Korea;Department of Pathology, School of Medicine, Ewha Womans University, Seoul, Korea;Department of Biological Science, Kongju National University, 182 Sinkwan-dong, Gongju 314-701, Korea;Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Korea;Department of Radiology, School of Medicine, Ewha Womans University, Seoul, Korea

关键词: Mitochondrial trifunctional protein (MTP);    HADHB;    Whole exome sequencing (WES);    Charcot-Marie-Tooth disease (CMT);   

Others  :  1127645
DOI  :  10.1186/1471-2350-14-125

 received in 2013-01-30, accepted in 2013-11-28,  发布年份 2013

【 摘 要 】

Background

Charcot-Marie-Tooth disease (CMT) is a heterogeneous disorder of the peripheral nervous system. So far, mutations in hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), beta subunit (HADHB) gene exhibit three distinctive phenotypes: severe neonatal presentation with cardiomyopathy, hepatic form with recurrent hypoketotic hypoglycemia, and later-onset axonal sensory neuropathy with episodic myoglobinuria.

Methods

To identify the causative and characterize clinical features of a Korean family with motor and sensory neuropathies, whole exome study (WES), histopathologic study of distal sural nerve, and lower limb MRIs were performed.

Results

WES revealed that a compound heterozygous mutation in HADHB is the causative of the present patients. The patients exhibited an early-onset axonal sensorimotor neuropathy without episodic myoglobinuria, and showed typical clinical and electrophysiological features of CMT including predominant distal muscle weakness and atrophy. Histopathologic findings of sural nerve were compatible with an axonal CMT neuropathy. Furthermore, they didn’t exhibit any other symptoms of the previously reported HADHB patients.

Conclusions

These data implicate that mutation in HADHB gene can also cause early-onset axonal CMT instead of typical manifestations in mitochondrial trifunctional protein (MTP) deficiency. Therefore, this study is the first report of a new subtype of autosomal recessive axonal CMT by a compound heterozygous mutation in HADHB, and will expand the clinical and genetic spectrum of HADHB.

【 授权许可】

   
2013 Hong et al.; licensee BioMed Central Ltd.

【 图 表 】

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