💬In plain words
What the trial is, and whether it could suit you
Background:
Amyotrophic lateral sclerosis type 4 (ALS4) is an inherited motor neuron disease. People with ALS4 have a change in the amount of RNA and DNA that bind together. This binding of RNA with DNA forms units called R-loops. Researchers want to learn how R-loops are related to ALS4. To do this, they will study people with inherited neurological conditions that may affect R-loop levels. These include ALS4, progressive external opthalmoplegia with mitochondrial deletions (PEOB2), Aicardi-Goutieres syndrome (AGS), and ataxia and oculomotor apraxia type 2 (AOA2).
Objective:
To learn how the binding of RNA with DNA (R-loops) is related to neurological disease.
Eligibility:
People age 5 and older with ALS4, PEOB2, AGS, and AOA2. Healthy relatives and nonrelatives are also needed.
Design:
Participants may be screened with a review of x-rays and other medical records.
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Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
* INCLUSION CRITERIA:
ALS4 RNA metabolism inclusion criteria:
* Age 5 or above
* Genetic diagnosis of ALS4 (heterozygous mutation in SETX)
* Able to communicate well with the investigator, to understand and comply with the requirements of the study
* Capacity to consent (adults) or assent (pediatric subjects) to the study
Disease control inclusion criteria:
* Age 5 or above
* Genetic diagnosis of RNA processing defect mutation (RNaseH1, RNaseH2, recessive mutations in SETX)
* Able to communicate well with the investigator, to understand and comply with the requirements of the study
* Capacity to consent (adults) or assent (pediatric subjects) to the study
Related, unaffected healthy control inclusion criteria:
* Age 5 or above
* Family history (first, second, or third degree relative) of RNA processing defect mutation (RNaseH1, RNaseH2, heterozygous or recessive mutations in SETX)
* Able to communicate well with the investigator, to understand and comply with the requirements of the study
* Capacity to consent (adults) or assent (pediatric subjects) to the study
Unrelated, healthy control inclusion criteria:
* Age 5 or above
* Able to communicate well with the investigator, to understand and comply with the requirements of the study
* Capacity to consent (adults) or assent (pediatric subjects) to the study
Gain of function inclusion criteria:
* Age 5 or above
* Genetic diagnosis of mutation resulting in a gain of function mechanism (for example, heterozygous mutations in SETX or heterozygous mutations in KCC3)
* Able to communicate well with the investigator, to understand and comply with the requirements of the studyCapacity to consent (adults) or assent (pediatric subjects) to the study
* Capacity to consent (adults) or assent (pediatric subjects) to the study
EXCLUSION CRITERIA:
ALS4 RNA metabolism exclusion criteria:
* Patients with known claustrophobia, presence of pacemaker, ferromagnetic material in their body, or any other condition that would preclude MRI assessments
* Pregnancy
Note: An Adult RNA metabolism ALS4 Patient who meets any of the following criteria will be excluded from the lumbar puncture procedure:
* PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
* INR greater than or equal to 1.5, thrombocytopenia (\<70,000), or abnormal bleeding time or platelet dysfunction
* History of a bleeding disorder
* Use of anticoagulants
* Disease control exclusion criteria:
--Pregnancy
* Related, unaffected healthy control exclusion criteria:
* Diagnosis of neuromuscular disease or weakness on physical examination
* Pregnancy
Note: An Adult Related, Unaffected Healthy Control who meets any of the following criteria will be excluded from the lumbar puncture procedure:
* PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
* INR greater than or equal to 1.5, thrombocytopenia (\<70,000), or abnormal bleeding time or platelet dysfunction
* History of a bleeding disorder
* Use of anticoagulants
* Unrelated, healthy control exclusion criteria:
* Diagnosis of neuromuscular disease or weakness on physical examination
* Patients with known claustrophobia, presence of pacemaker, ferromagnetic material in their body, or any other condition that would preclude MRI assessments
* Pregnancy
Note: An Adult Unrelated, Healthy Control who meets any of the following criteria will be excluded from the lumbar puncture procedure:
* PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
* INR greater than or equal to 1.5, thrombocytopenia (\<70,000), or abnormal bleeding time or platelet dysfunction
* History of a bleeding disorder
* Use of anticoagulants
Gain of function exclusion criteria:
-Pregnancy
Note: An Adult Gain of Function patient who meets any of the following criteria will be excluded from the lumbar puncture procedure:
* PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
* INR greater than or equal to 1.5, thrombocytopenia (\<70,000), or abnormal bleeding time or platelet dysfunction
* History of a bleeding disorder
* Use of anticoagulants
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