title: A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-tooth disease.
abstract: 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.
authors: Young Bin
authors: YB
authors: Hong
authors: Ja Hyun
authors: JH
authors: Lee
authors: Jin-Mo
authors: JM
authors: Park
authors: Yu-Ri
authors: YR
authors: Choi
authors: Young Se
authors: YS
authors: Hyun
authors: Bo Ram
authors: BR
authors: Yoon
authors: Jeong Hyun
authors: JH
authors: Yoo
authors: Heasoo
authors: H
authors: Koo
authors: Sung-Chul
authors: SC
authors: Jung
authors: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong Gangnam-Gu, Seoul 135-710, Korea. kwchung@kongju.ac.kr.
authors: Ki Wha
authors: KW
authors: Chung
authors: Byung-Ok
authors: BO
authors: Choi
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002607:Charcot-Marie-Tooth Disease / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D002648:Child; D059472:Exome; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D007866:Leg / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D063991:Mitochondrial Trifunctional Protein / Q000172:deficiency; D063993:Mitochondrial Trifunctional Protein, beta Subunit / Q000235:genetics*; D009133:Muscular Atrophy / Q000209:etiology / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D011115:Polyneuropathies / Q000209:etiology / Q000235:genetics; D013497:Sural Nerve / Q000473:pathology; D055815:Young Adult
chemical_list: C576206:HADHB protein, human; D063991:Mitochondrial Trifunctional Protein; D063993:Mitochondrial Trifunctional Protein, beta Subunit