An Observational Study to Assess Clinical Manifestations and Biomarkers in Amyotrophic Lateral Sclerosis Type 4, Other Inherited Neurological Disorders With RNA Processing Defects, and Other Neurological Diseases With a Gain of Function Mechanism.

Summary

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. 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. ...

Description

Eligibility

Age range

5–120 years

Sex

All

Healthy volunteers

Yes

Location