Gene Mutation Analysis Of A Special Charcot-Marie-Tooth Disease Family With Type2Diabetes Mellitus

[Background and objective]Charcot-Marie-Tooth (CMT) disease, also known as hereditary motor and sensory neuropathies (HMSN), is genetically heterogeneous and characterized by slowly progressive distal muscle wasting and weakness with sensory loss. It is the most common inherited disorder of the peripheral nervous system with an estimated prevalence of1in2.500. CMT is generally subdividied into demyelinating CMT1and axonal CMT2on the basis of nerve conduction velocity. The motor nerve conduction velocities(MNCV) of the median nerve is less than38m/s in CMT1patients, whereas that is normal or near normal in CMT2.The majority of CMT are autosomal dominant inheritance, but someone also showed autosomal recessive or X-linked inheritance. The object of this research is to investigate the clinical features and possible molecular biological mechanism of a Charcot-Marie-Tooth disease family with Type2Diabetes Mellitus.[Methods]40members from a CMT family was studied, who underwent detailed family line investigation, clinical examination, laboratory and electromyography examination, The blood samples of23members (4CMT patients,11kinship members,7unrelated members) were collected and stored. The duplication of the peripheral myelin protein22(PMP22) gene was examined by using Real Time PCR. The PMP22and myelin protein zero (MPZ) mutation were screened by the use of PCR combined with direct sequencing in twenty three family members.[Results] This is a family with autosomal dominant CMT neuropathy phenotypes, majority of patients were puberty onset. The anticipation phenomenon can be shown in this family. Five patients of the family were diagnosed as CMT1, four of them with Type2Diabetes Mellitus. Most of them had manifested distal muscle wasting and weakness, sensory loss, abnormal gait with reduced tendon reflexes. The motor nerve conduction velocities(MNCV) of the median nerve are less than38m/s in four patients and two suspect patients. Gene mutation analysis does not show any large fragment duplication or point mutations of PMP22in23members; An5820A to G synonymous point mutation of MPZ was identified in one CMT1patient(Ⅲ1) with Type2Diabetes Mellitus.[Conclusions]1)It is the first report of clinical and molecular study of CMT with Type2Diabetes Mellitus family pedigree in China;2) Large fragment duplication of PMP22is not the genetic cause of this CMT family;3)The5820A to G synonymous point mutation of MPZ is not the genetic cause of this family;4) Further research shoud be studied on the mitofusin2(Mfn2) gene mutation which is related to CMT2and Type2Diabetes Mellitus,.