Clinical Features And Genetics Of Two CMTX1 Families

Objective:Clinical and genetics analysis to two probable X-linked dominant Charcot-Marie-Tooth disease families which,in probands,appeared paroxysmal symptoms with cerebral white matter abnormalities in brain MRI.So as to identify diagnosis and molecular genetics etiological factor,and analyse possible pathogenesis causing the transient symptoms and CNS impairment.Methods:Both probands were taken medical examination,body fluid examination,brain MRI Imageology examination,EMG,nerve conduction velocity(NCV)examination,gastroc and sural nerve neurohistology,semithin section and ultramicrostructure pathology examination. PCR for GJB1 gene exon region and sequencing to the proband P1,P2 and their parents and several healthy controls extra of the two families.Looking for the causive mutation,then by restriction enzyme cutting reaction confirming the mutation.At last all relative medical and genetics research results are been analized comprehensively,draw some conclusion,and analyse the possible pathogenesis.Results:①Clinical examinations:Proband P1 and P2 both ever suffered from paroxysmal aphasia et al symptoms.They were not amyosthenia and atrophy in distal extremity but there both existed areflexia of achilles reflex suggesting peripheral nerve damage.In each family,males are more severe than females clinically.The both probands also were found some abnormal immunology indexes.②Electrophysiology:the two probands both revealed nerve damages in peripheral nerve.Median nerve conduction velocity reduced in a middle degree.There were not obviously nerve damage detected in the proband P2 's mother.③Brain MRI Imageology:by brain MRI during the episodes,the two probands both revealed multiple abnormal signals in bilateral brain white matter.and in proband P1,the white matter lesions apparently reduced comparatively in two month and four month after the last episode. The rechecking result of proband P2 was not obtained.④Gastroc and sural nerve pathology:Two probands both revealed chronic axonal peripheral neuropathy accompanied by lower grade demyelination.And nerve dropsy and flaming change was discovered in sural nerve semithin section of proband P1.⑤Molecular genetics:p.Arg15Trp was found in the proband P1.p.Arg75Trp was found in the proband P2.and the same mutations as their sons also were found in their mothers in heterozygote type,but not in their fathers and several normal controls out of the family,The both mutations both are of known pathogenic mutations in the human gene mutation database. Conclusions:The two probands and their own familys both suffer from the X-linked dorminant Charcot-Marie-Tooth disease.The Arg15Trp missence mutation may cause episodes of CNS symptoms with transient cerebral brain white abnormality which relation may be the first report in the world.The Arg75Trp missence mutation may cause episodes of motor aphasia with cerebral brain white abnormality which relation may be the first report in China.