This study is currently recruiting participants.
Number
20-N-0064
Sponsoring Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 5 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
None
Keywords
Natural History Study; Biomarker Development; Natural History
Recruitment Keyword(s)
Condition(s)
Amyotrophic Lateral Sclerosis Type 4; Inherited Neurological Disorders of RNA Processing
Investigational Drug(s)
Investigational Device(s)
Intervention(s)
Supporting Site
National Institute of Neurological Disorders and Stroke
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.
Healthy relative and nonrelative participants will have 1 visit. All other participants will have 4 visits over 3 years.
At visits, participants will undergo some or all of the following:
Medical history
Physical exam
Tests of muscle strength and volume and physical function
Blood tests
Pregnancy test (for some females)
Skin biopsy of forearm
Magnetic resonance imaging (MRI)
Dual x-ray absorptiometry (DEXA).
Some tests are optional.
The MRI uses a magnetic field and radio waves to take pictures. Participants will lie on a table that slides in and out of the scanner. The scanner makes noise. They will get earplugs.
The DEXA scan uses x-rays to take pictures.
MRI and DEXA will be used to measure muscle, fat, and lean body mass.
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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
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:
-Genetic diagnosis of RNA processing defect mutation (RNaseH1, RNaseH2, recessive mutations in SETX)
Related, unaffected healthy control inclusion criteria:
-Family history (first, second, or third degree relative) of RNA processing defect mutation (RNaseH1, RNaseH2, heterozygous or recessive mutations in SETX)
Unrelated, healthy control inclusion criteria:
Gain of function inclusion criteria:
-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
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
Note: An Adult Related, Unaffected Healthy Control who meets any of the following criteria will be excluded from the lumbar puncture procedure:
---History of a bleeding disorder
-Unrelated, healthy control exclusion criteria:
--Patients with known claustrophobia, presence of pacemaker, ferromagnetic material in their body, or any other condition that would preclude MRI assessments
Note: An Adult Unrelated, Healthy Control who meets any of the following criteria will be excluded from the lumbar puncture procedure:
Gain of function exclusion criteria:
Note: An Adult Gain of Function patient who meets any of the following criteria will be excluded from the lumbar puncture procedure:
Principal Investigator
Referral Contact
For more information: