Genetics of Charcot Marie Tooth (CMT) - Modifiers of CMT1A, New Causes of CMT2

Официальное название

Genetics of Charcot Marie Tooth Disease (CMT) - Modifiers of CMT1A, New Causes of CMT

Обзор

This project includes two projects. One is looking for new genes that cause Charcot Marie Tooth disease (CMT). The other is looking for genes that do not cause CMT, but may modify the symptoms a person has.

Подробное описание

This project is to understand modifier genes and how they influence the severity of disease expression, along with identifying new forms of CMT which have not been genetically determined. Subjects who are eligible will either have CMT type 1A (CMT1A) or an unknown form of CMT. Blood will be drawn and sent to the University of Miami where they receive the coded sample and process it through exome sequencing. Subjects will be told that this is optional.

Первичные конечные точки

• Charcot Marie Tooth disease type 1A (CMT1A) gene modifiers [Срок оценки: once]
• New genetic causes of CMT [Срок оценки: Once]

Критерии участия

Критерии включения

All patients must agree to take part in the study and sign a consent form. A teenager (age 13-17 years) considering enrolling must agree to take part in the study and sign an assent form (depending on local ethics committee requirements).

Additional inclusion criteria are described below.

Inclusion Criteria: CMT1A Gene Modifier Study

Patients must have at least one of the following:

• Patient has a documented PMP22 duplication. AND/OR
• Patient has a first or second degree relative (parent, child, sibling, half- sibling, aunt, uncle, grandparent, grandchild, niece, or nephew) with a documented PMP22 duplication AND a clear link between that family member and the affected patient AND a phenotype consistent with CMT1A.

i. A clear link is necessary for a second-degree relative. For example, if a grandparent is affected and has a PMP22 duplication, and the parent does not have any signs, symptoms, or electrophysiology consistent with CMT1A, there is no clear link.

ii. In cases where clear links are not available, genetic testing is required for the patient or the first degree family member who is not clearly affected.

Inclusion Criteria - Patients for CMT Exome Project

a. Patient has demonstrated neuropathy on nerve conduction studies or clinically diagnosed genetic neuropathy, in the opinion of the investigator or genetic counsellor.

Inclusion Criteria - Controls for CMT Exome Project

• Person is a family member of a CMT patient who is enrolled in the CMT Exome Project.

AND one of the following:

• Person does not have a peripheral neuropathy, in the opinion of the investigator or genetic counsellor.

OR

• Person is suspected to have a peripheral neuropathy, but has not been examined at an INC site.

Критерии исключения

• Patient does not wish to participate or does not sign a consent form.
• For CMT Exome Project, patient has a genetically confirmed form of CMT (i.e. mutation in MFN2 causing CMT2A, mutation in GARS causing CMT2D, etc.).
• Patients with known neuropathy from a non-genetic source, such as chemotherapies (i.e. Vincristine, Taxol, Cisplatin), diabetes, alcoholism will be evaluated independently so that genetic contributions to their effects on CMT1A phenotypes can also be analyzed.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 17 центров

• Cedars-Sinai Medical Center — Los Angeles
• Stanford University — Palo Alto
• University of Colorado Hospital — Aurora
• Connecticut Children's Medical Center — Hartford
• University of Miami — Miami
• University of Iowa — Iowa City
• Johns Hopkins University — Baltimore
• Harvard/Massachusetts General Hospital — Boston
• … и ещё 9 центров

Великобритания · 2 центра

• National Hospital of Neurology and Neurosurgery — London
• Dubowitz Neuromuscular Centre — London

Австралия · 1 центр

• Children's Hospital of Westmead — Sydney

Канада · 1 центр

• The Hospital for Sick Children — Toronto

Италия · 1 центр

• C. Besta Neurological Institute — Milan

Публикации

• Montenegro G, Powell E, Huang J, Speziani F, Edwards YJ, Beecham G, Hulme W, Siskind C, Vance J, Shy M, Zuchner S. Exome sequencing allows for rapid gene identification in a Charcot-Marie-Tooth family. Ann Neurol. 2011 Mar;69(3):464-70. doi: 10.1002/ana.22235. Epub 2011 Jan 20. PMID 21254193

Идентификаторы

NCT: NCT01193088 · INC-6602 · 1U54NS065712-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗