Myotubular Myopathy Genetic Testing Study

• Prospective participants will complete registration in the CMDIR.
• The CMDIR genetic curator will review CMDIR data for study eligibility.
• If eligible, participant will be called and consented to participate in the study.
• Sequencing can be done with a saliva sample. However, if this method does not detect a mutation or change in the MTM1 gene, a further test, called CGH Array, has to be performed. For the CGH Array test, a saliva sample may deliver a clear result in terms of a deletion/duplication mutation. In the event, CGH Array with the saliva sample does not provide a result, a the blood sample is necessary to repeat CGH Array.
• The study participant will receive a kit and instructions for saliva specimen collection for genetic testing from the CMDIR in the mail.
• If a mutation or change in the MTM1 gene could not be found by genetic testing and CGH Array with a saliva sample, the study participant will receive a second kit in the mail from the CMDIR with instructions for a blood draw to be used for CGH Array.
• The family will coordinate collection of the saliva specimen or a local blood draw, if necessary, and will be responsible for mailing the specimen in a pre-paid parcel to the University of Chicago. There will be a $40 reimbursement for the cost of the blood draw. Mailing the specimen to the testing site is at no cost for the participant. A two-week turn-around from receipt of the kit to sending it to the testing laboratory is requested.
• Genetic testing will start with standard sequencing of the MTM1 gene, isolated from the saliva specimen, followed by CGH Array if sequencing of the MTM1 gene isolated from the saliva sample or further from a blood sample if a variant consistent with the symptoms could not be detected using the saliva sample.
• Test results will be 1) reported to a physician specified by the study participant and 2) uploaded into the study participant's profile in the CMDIR and 3) if concurrently enrolled in the Beggs Laboratory or other IRB-approved clinical study, test results will also be made available to that study provided appropriate informed consent has been given.

Inclusion criteria

Patient eligibility will be determined by the CMDIR genetic curator using the following prioritization protocol.

• Males and females in the US and Canada who have a known mutation in the MTM1 gene identified in a research lab and never confirmed in a clinical CLIA (Clinical Laboratory Improvement Amendments) -certified laboratory.
• Male and female patients in the US and Canada who meet 2 of 3 of the following criteria: + clinical history, + family history, + centronucleation on muscle biopsy (no signs of nemaline rods or cores). Clinical history includes: post-natal breathing support (not necessarily continued after first month), length above 90% for EGA (estimated gestational age), facial characteristics (narrow facies), facial weakness (ophthalmoplegia, excessive saliva with need for suctioning).
• Males and females in the US and Canada who present with XLMTM symptoms and no genetic mutation in the MTM1 gene found with conventional sequencing, requiring CGH array deletion/duplication testing.
• Age range: One month - no maximum age.
• Individual is registered with the CMDIR.
• Written study consent provided by parent/caregiver (affected individual's age less than 18 years or for those individuals greater than 18 years with learning disabilities or inability to physically access consent) or affected individual (age greater than 18 years)

Exclusion criteria

• Carrier testing for asymptomatic mothers.