Genetics of Charcot-Marie-Tooth Dystrophy and Related Diseases

This is a cross-sectional study to clarify the gene lineage distribution of CMT genes in CMT patients in my country, draw a frequency map of CMT gene distribution, and assist in determining the genetic diagnosis strategy of CMT diseases. All patients will be collected for clinical and electrophysiological data. Patients and families who meet the enrollment criteria will be tested for blood tests.

Study Overview

• Status: Recruiting
• Conditions: Peroneal Muscular Atrophy
• Intervention / Treatment: Other: basic information; Other: venous blood test

Detailed Description

[Background] Peroneal muscular atrophy (Charcot-Marie-Tooth, CMT) is a group of the most common hereditary peripheral neuropathy, with a prevalence of about 1/2500-4000. The inheritance mode can be autosomal dominant inheritance, autosomal recessive inheritance, X-linked dominant inheritance and X-linked recessive inheritance. The typical clinical manifestations are progressive, length-dependent weakness and atrophy of the distal limbs, accompanied by hypoesthesia and weakened tendon reflexes. But the generalized peroneal muscular atrophy also includes hereditary motor neuropathy and hereditary sensory neuropathy, which represents the evolution of a disease spectrum from motor nerve to motor sensory nerve and sensory nerve, collectively referred to as CMT and its related diseases. CMT can be divided into demyelinating type (CMT1), axonal type (CMT2) and intermediate type. There are more than 80 kinds of genes discovered so far, and genetic diagnosis plays a vital role in the treatment of peroneal muscular atrophy and genetic counseling.

[Purpose]

1. To clarify the gene lineage distribution of CMT genes in CMT patients in my country, draw a frequency map of CMT gene distribution, and assist in determining the genetic diagnosis strategy of CMT diseases;
2. Discover new mutations and newly published types of known genes, and perform gene-phenotype correlation analysis
3. Perform whole-exome sequencing on some families that have not been clearly diagnosed to find new pathogenic genes or related genes of CMT, so as to enrich the genetic and clinical types of CMT.

[Design] This is a cross-sectional study. All patients will be collected for clinical and electrophysiological data. Patients and families who meet the enrollment criteria will be tested for blood tests. The inspection strategies are as follows: (1) Use MLPA method for PMP22 gene Duplicate or deletion mutation check (charge); (2)) Use high-throughput sequencing method to detect the currently known gene panel (gene panel) (charge); (3) Check the process (1) and (2) Some patients and families whose disease-causing genes have not been detected by the inspection methods are tested by whole-exome sequencing (scientific research, free of charge).

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Xiaoxuan Liu; Phone Number: 13910982101; Email: zhangys0317@126.com
• Study Contact Backup: Name: Xiaoxuan Liu; Email: zhangys0317@126.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Peroneal muscular atrophy is a group of genetic diseases with very high genetic heterogeneity that violates the peripheral nervous system. The typical clinical manifestations are progressive, length-dependent limb weakness and atrophy, accompanied by hypoesthesia and weakened tendon reflexes.

Description

Inclusion Criteria:

• Meet the clinical diagnostic criteria of peroneal muscular atrophy; Sign informed consent

Exclusion Criteria:

• Those who have recently received blood transfusion treatment will not be able to collect blood samples.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Peroneal muscular atrophy; Peroneal muscular atrophy (Charcot-Marie-Tooth, CMT) is a group of genetic diseases that invade the peripheral nervous system with very high genetic heterogeneity. It was proposed by Charcot, Marie of France and Tooth of the United Kingdom in 1886. The prevalence is about 1/2500-4000. It is the most common hereditary peripheral neuropathy. Inheritance includes all forms of Mendelian inheritance. The typical clinical manifestations are progressive, length-dependent limb weakness and atrophy, accompanied by hypoesthesia and weakened tendon reflexes.

Other: basic information; Demographic data registration, medical history inquiry, physical examination; electromyography, nerve conduction velocity examination; CMT nerve function score; Other: venous blood test; The specific method is as follows: 12ml of peripheral blood is drawn from the peripheral vein, and EDTA is used for anticoagulation. No fasting is required before blood draw, and there is no time limit. Part of the specimens submitted for inspection are sent to a qualified genetic testing company for examination, and the fees are charged in accordance with the corresponding charging standards set by the hospital. The remaining part of the sample will be stored or accumulated for a period of time, and the DNA will be extracted and stored in the sample library.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
allele frequency of CMT genes	Observed values of allele frequency of CMT genes	1 month
genotype frequency of CMT genes	Observed values genotype frequency of CMT genes	1 month

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Investigators: Principal Investigator: Xiaoxuan Liu, Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: June 27, 2021
• First Submitted That Met QC Criteria: July 12, 2021
• First Posted (Actual): July 19, 2021

Study Record Updates

• Last Update Posted (Actual): July 19, 2021
• Last Update Submitted That Met QC Criteria: July 12, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Congenital Abnormalities; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Heredodegenerative Disorders, Nervous System; Atrophy; Nervous System Malformations; Polyneuropathies; Muscular Atrophy; Nerve Compression Syndromes; Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy
• Other Study ID Numbers: M2018206

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No