Associated genes with early and late onset of symptoms in patients with Charcot–Marie–Tooth disease

سال انتشار: 1398
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 476

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شناسه ملی سند علمی:

GCMED08_005

تاریخ نمایه سازی: 10 دی 1398

چکیده مقاله:

Background and Aim : Charcot–Marie–Tooth (CMT) is a common polyneuropathy and genetically heterogeneous disease with mutations in 70 known genes. This disorder is characterized by muscle wasting, sensory loss, insidious onset of distal predominant motor, and Skeletal deformations. Based on inheritance and neurophysiologic investigations, there are three subtypes of CMT; CMT1 is demyelinating, CMT2 axonal, and intermediate CMT mixed. Due to CMT s clinical and molecular heterogeneity and shortcomings of previous diagnostic tests many families remained without a molecular diagnosis. Recently the use of whole exome sequencing (WES), combined with multigene testing panels, have increased the sensitivity and efficiency of genetic testing for detecting known or novel mutations in CMT families. Methods : Here we used WES for identifying variations through CMT associated genes in two Iranian patients. The first patient was a 3-year old female with speech impediments, strabismus, splenomegaly, clinodactyly of the fifth fingers, abnormal hands and foots, and conical teeth, who had been diagnosed with autism. The second patient have diagnosed with hypotonia in infancy and lately with clinodactyly, hand tremors and distal wasting of the legs. The last patient was 34 years old male has spastic paraplegia features and one of his siblings had been died at age of 18 due to motor impairment, scoliosis and pulmonary disease. Because the patients parents were consanguineous, they have been enrolled for co-segregation analysis. Results : Through WES of the cases we identified homozygous c.A638G and c.449+1G> T in the IGHMBP2 gene of first and second patients. Both variants have been previously reported as pathogenic and main cause of CMT disease. In the third patient we detected a novel large homozygous deletion of exon 2-6 in the MPZ gene. Our bioinformatic analysis showed that this deletion can be deleterious. The variants co-segregated through the patient s relatives, suggesting hereditary pattern of CMT. Conclusion : According to our results, it seems that the IGHMBP2 pathogenic mutations may associate with early onset CMT while the MPZ variations linked to the late onset CMT disease.

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نویسندگان

Maryam Rezazadeh

Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran۱. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Jalal Gharesouran

Molecular Genetics Division, GMG center, Tabriz, Iran