Mutations in Genes Associated With Pentalogy of Cantrell

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.

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Key information

Conditions

Pentalogy of Cantrell Abnormalities, Multiple Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities MYH9-Related Disorders Nervous System Diseases Nervous System Malformations Neural Tube Defects

Age range

Up to 100 year

Sex eligibility

All sexes

Study type

Observational

Primary location

National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

INCLUSION CRITERIA:

i. Index Cases

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.
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.

ii. Relatives of Index Cases

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.
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:

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.
Research use of the fetal tissue in accordance to NIH Division of Intramural Research (DIR) Program fetal tissue policy guidelines:

No profits will be involved;
NIH researchers will have no involvement in the termination of pregnancy, and
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.

Treatment and study plan

Primary outcomes

Identify the gene(s) mutation (s) that causes Pentalogy of Cantrell

Time frame: ongoing

Identification of novel genes related to Pentalogy of Cantrell

Secondary outcomes

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.
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.

Sponsors and collaborators

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Nih

Registry information

Important dates

Study start: 2004
Primary completion: 2019
Study completion: 2019
First posted: May 25, 2004
Registry last updated: Oct 8, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed