Publications (2)5.5 Total impact
-
Article: -459C>T point mutation in 5' non-coding region of human GJB1 gene is linked to X-linked Charcot-Marie-Tooth neuropathy.
[show abstract] [hide abstract]
ABSTRACT: Charcot-Marie-Tooth (CMT) neuropathy is inherited with genetic and clinical heterogeneity. The X-linked form (CMTX) is linked to mutations in the GJB1 gene. However, the genotype-phenotype correlation between variants in the non-coding region of GJB1 gene and CMTX is unclear. We found two structural variants (-459C>T and -713G>A) in the 5' non-coding region of a transcript (Ref seq ID: NM_000166) of the GJB1 gene and explored its association with CMTX in two Chinese families. All family members who carried the -459C>T variant either were symptomatic or had abnormal electrophysiological studies compatible with CMTX, whereas all the non-symptomatic family members who had normal electrophysiological studies and 10 healthy unrelated controls did not have this variant. The other variant in the 5'-flanking region of the gene was found to be a benign polymorphism, although it had been earlier reported to be associated with CMTX in a Taiwanese family. Secondary structure prediction analysis of mutant mRNA using M fold and RNA structure softwares indicates that the -459C>T mutation may reduce translation efficiency of the GJB1 gene by changing its 5'-untranslated region secondary structure and abolishing the internal ribosome entry site at the initialization of its translation in Schwann cells. Our study can help clarify the causal mutations of CMTX in the non-protein coding region of GJB1.Journal of the Peripheral Nervous System 04/2009; 14(1):14-21. · 2.80 Impact Factor -
Article: Abnormal diffusion tensor in nonsymptomatic familial amyotrophic lateral sclerosis with a causative superoxide dismutase 1 mutation.
[show abstract] [hide abstract]
ABSTRACT: To determine whether diffusion abnormalities can be observed in nonsymptomatic family members with a known causative Cu/Zn superoxide dismutase mutation (asymptomatic familial amyotrophic lateral sclerosis; AFALS(+SOD1)) in a family with autosomal dominant familial amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI). A total of eight AFALS(+SOD1) subjects (aged 17-43 years) were age-matched with 13 healthy controls (aged 19-45 years) without SOD1 mutations. DTI was carried out on a 1.5T scanner. The diffusion index maps derived were then normalized spatially for voxel-based analysis. region of interest (ROI)-based analysis was also carried out. Our voxel-based and ROI-based analysis showed that AFALS(+SOD1) subjects have decreased fractional anisotropy (FA) (0.5401 vs. 0.5168, P < 0.05) and increased tensor trace (TT) (2.5854 x 10(-3) mm(2)/second vs. 2.6226 x 10(-3) mm(2)/second, P < 0.04) at the posterior limb of the internal capsule compared to the control subjects. Increased radial diffusivity (E((2,3)/2)) was detected on both sides (right = 0.5710 x 10(-3) mm(2)/second vs. 0.5943 x 10(-3) mm(2)/second, P < 0.05; left = 0.5666 x 10(-3) mm(2)/second vs. 0.5872 x 10(-3) mm(2)/second, P < 0.05). No significant change in axial diffusivity (E(1)) was detected. Abnormal diffusivity was found at the posterior limb of the internal capsule in AFALS(+SOD1) subjects, hitherto unreported. Our results suggest that DTI may detect diffusion abnormalities in AFALS(+SOD1) subjects before symptoms develop.Journal of Magnetic Resonance Imaging 01/2008; 27(1):8-13. · 2.70 Impact Factor
