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Mutations in Genes Associated With Pentalogy of Cantrell

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ClinicalTrials.gov Identifier: NCT00083499
Recruitment Status : Recruiting
First Posted : May 25, 2004
Last Update Posted : April 11, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Brief Summary:

This study will collect blood, urine, and other tissue samples from patients with Pentalogy of Cantrell (POC) and other inherited diseases that may involve mutations in non-muscle myosin II-B heavy chain (MYH10). We will also collect samples from the relatives of affected individuals. POC is a very rare disorder in which patients have a combination of severe defects of the middle of the chest including the sternum (breastbone), diaphragm, heart, and abdominal wall. The defect are apparent before birth or at birth.

Participants may undergo a medical evaluation that could include a medical history routine blood tests, urine collection, chest x-ray, and electrocardiogram. In addition, blood, urine, saliva, buccal swab or tissue samples may be collected for protein and gene studies. The blood is drawn through a very small needle placed in an arm vein. Children may choose to have a buccal (cheek) sample taken instead of blood draw. Buccal samples can be collected by a cheek swab, in which a soft brush is rubbed on the inside lining of the mouth, or by having the child hold a tablespoon of mouthwash in his or her mouth for a full minute and then spit the mouthwash into a container. In addition, tissue samples may be collected from patients if they undergoing any surgical procedures that may be required as part of their general medical care.

Some of the cells obtained from patients or their relatives may be used to establish cell lines (a living tissue sample) that can be grown in the laboratory and used for experiments.


Condition or disease
Pentalogy of Cantrell

Detailed Description:
The purpose of this multisite protocol is to collect protein, DNA, and RNA from blood, sputum, urine and/or tissue samples from patients with the diagnosis of Pentalogy of Cantrell (POC) or other related syndromes in order to identify possible causative genes. We will use whole exome/genome sequencing of probands, their parents, and, if available, the affected relatives of probands to look for any exomic/genomic mutations that could be associated with this syndrome. We have produced a mouse model with the mutant mice exhibiting problems with ventral wall closure including extrathoracic location of the heart (ectopia cordis), and defects in the abdominal wall with protrusion of the guts and liver. The mice, which have a single amino acid substitution in nonmuslce myosin II-B, have severe defects in both the heart and brain, and resemble humans born with POC, who manifest these same abnormalities.

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Family-Based
Time Perspective: Cross-Sectional
Official Title: Mutations in Genes Associated With Pentalogy of Cantrell
Actual Study Start Date : September 15, 2004

Resource links provided by the National Library of Medicine


Group/Cohort
Group 1
Index cases
Group 2
Relatives of Index Cases
Group 3
Fetal tissue



Primary Outcome Measures :
  1. Identify the gene(s) mutation (s) that causes Pentalogy of Cantrell [ Time Frame: ongoing ]
    Identification of novel genes related to Pentalogy of Cantrell


Secondary Outcome Measures :
  1. Since mutations in NM IIB may not be the sole cause of POC, we also intend to identify any other gene(s) mutation(s) that might be thecause of POC. [ Time Frame: Ongoing ]
    Identifying any other gene(s) mutation(s) that might be the cause of POC.

  2. We may wish to procure tissues from patients with nonmuscle myosin IIA and IIC mutations in order to study the mechanism underlyingthese abnormalities. [ Time Frame: Ongoing ]
    Studying the mechanism underlying these abnormalities in procuredtissues from patients with nonmuscle myosin IIA and IIC mutations.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 100 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Primary clinical
Criteria
  • INCLUSION CRITERIA:

    i. Index Cases

    1. Those patients who have a diagnosis of POC or other related syndromes (as defined under Study Design) confirmed by telephone discussion between the investigators and the patient s physician.
    2. Outside Institutions- All ages will be included
    3. At the Clinical Center - Those subjects that are greater than or equal to 2 years of age and older.

ii. Relatives of Index Cases

  1. We may obtain samples from family members and/or relatives of those individuals who have a diagnosis of POC or other related syndrome confirmed by telephone discussion between the investigators and the referring physician with knowledge of the index case.
  2. Outside Institutions - All ages will be included. At the Clinical Center - Those subjects that are greater than or equal to 2 years of age and older

iii. Fetal tissue:

  1. We may obtain samples from patients with a fetal diagnosis of POC or other related syndrome with diagnosis confirmed by telephone discussion between the investigators and the referring physician.
  2. Research use of the fetal tissue in accordance to NIH Division of Intramural Research (DIR) Program fetal tissue policy guidelines:

    1. No profits will be involved;
    2. NIH researchers will have no involvement in the termination of pregnancy, and
    3. The tissue must be obtained in accordance with Federal, state, and local law including those that govern basic research using human fetal tissue and research involving the transplantation of fetal tissue.

EXCLUSION CRITERIA:

Subjects seen at the Clinical Center - Those subjects that are less than or equal to 2 years of age and older.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00083499


Contacts
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Contact: Sandra D MacDonald, R.N. (301) 451-4899 macdonas@nhlbi.nih.gov
Contact: Robert S Adelstein, M.D. (301) 496-1865 adelster@nhlbi.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Robert S Adelstein, M.D. National Heart, Lung, and Blood Institute (NHLBI)

Additional Information:
Publications:
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Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00083499     History of Changes
Other Study ID Numbers: 040202
04-H-0202
First Posted: May 25, 2004    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: March 27, 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
Nonmuscle myosin IIB
Nonmuscle myosin IIA
Pentology of Cantrell
thoracoabdominal syndrdome
Nonmuscle Myosin IIC
Pentalogy of Cantrell
Non-muscle Myosin Heavy Chain Genes

Additional relevant MeSH terms:
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Pentalogy of Cantrell
Neural Tube Defects
Nervous System Malformations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities