Genetic Causes of Growth Disorders
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|ClinicalTrials.gov Identifier: NCT02311322|
Recruitment Status : Recruiting
First Posted : December 8, 2014
Last Update Posted : April 1, 2019
- Some growth disorders are caused by a change in genes. Genes are the instructions the body uses to function. Changes in genes often cause them not to work correctly. Researchers want to use a new technology called exome sequencing, to look at many genes at once. This is done by looking at DNA from blood or saliva in a lab. This method may help find the cause of disorders that researchers haven t been able to find using past methods.
- To better understand genetic causes of growth disorders.
- Children and adults with growth disorders and their family members.
- Participants will give a small sample of blood and/or saliva.
- Researchers will purify DNA from the sample. They will perform exome sequencing and other tests to look for changes in genes. Some participants may receive limited or no genetic tests. Researchers will let them know if exome sequencing is performed.
- Participants may have a medical history, physical exam, and lab tests. They may have x-rays or ultrasound tests to study the disorder in their family.
- Some participants may be recommended for a specific genetic test from a commercial lab. They may have to pay for that test.
- Participants will be told about test results that relate to the growth disorder. This may happen up to years after the testing. They may have to give another blood and/or saliva sample.
- Some participants may get results about other health conditions. This will only happen if the information would help the person or their family protect their health. They may have to give another blood and/or saliva sample.
|Condition or disease|
|Short Stature Growth Disorder|
Children often present to pediatricians and pediatric endocrinologists because of abnormal body growth, including both childhood growth failure and, less commonly, overgrowth. Sometimes the cause is evident, for example, growth hormone deficiency for growth failure and growth hormone excess for overgrowth. In other children, the etiology remains unknown despite extensive evaluation, resulting in the unhelpful diagnosis of severe idiopathic short stature or tall stature. These conditions are quite heterogeneous, including children with isolated growth disorders and others who also have other abnormalities such as developmental delay or a constellation of congenital anomalies (syndromic growth disorders). Some cases of severe growth disorders have a polygenic inheritance while others appear to be inherited as a monogenic trait recessive, dominant or X-linked. Because of recent advances in DNA sequencing technology, it is now feasible to sequence the exome (portion of the genome that encodes gene exons) in families with monogenic disorders and thereby determine the underlying molecular etiology.
We therefore propose a study to identify novel genetic causes of idiopathic growth disorders using whole-exome sequencing. The primary goal of this study is to identify novel causes of childhood growth disorders in order to improve clinical diagnosis, to provide a more precise characterization of associated medical problems, prognosis, and response to treatment based on etiology, and to gain new insights into the regulation of human growth, which may eventually lead to new therapeutic approaches.
Subjects will include children and adults with a clearly recognizable phenotype that includes either short stature or tall stature and a pedigree that strongly suggests a monogenic inheritance. Both syndromic and non-syndromic growth disorders and both proportionate and disproportionate growth disorders will be included. Affected and unaffected family members (who have informative meiotic inheritance relationships to the proband or index case) will also be studied because of their importance for this genetic approach. The phenotype will be characterized by medical history, physical exam, body measurements, and laboratory evaluation. Blood and saliva samples will be collected for whole-exome sequencing and single nucleotide polymorphism (SNP) array analysis. Candidate sequence variants will typically be verified by Sanger sequencing.
|Study Type :||Observational|
|Estimated Enrollment :||800 participants|
|Official Title:||Genetic Causes of Growth Disorders|
|Study Start Date :||December 5, 2014|
|Estimated Primary Completion Date :||December 31, 2024|
|Estimated Study Completion Date :||December 31, 2024|
Children with growth disorders
Family members of subjects with growth disorders
- SNP array and whole exome sequencing data [ Time Frame: 12 months ]identification of the causal variant
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02311322
|Contact: Youn H Jee, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institute of Child Health and Human Development (NICHD)||Recruiting|
|Bethesda, Maryland, United States, 20892|
|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 email@example.com|
|Principal Investigator:||Youn H Jee, M.D.||Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|