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Protocol Details

Genetic Analysis of Brain Disorders

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Human Genome Research Institute (NHGRI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 1 mo
Max Age: N/A

Referral Letter Required


Population Exclusion(s)


Special Instructions

Currently Not Provided


Agenesis of Corpus;
Genetic Tests

Recruitment Keyword(s)




Investigational Drug(s)


Investigational Device(s)




Supporting Site

National Human Genome Research Institute

A study of the complex genetics of brain development will be undertaken with an emphasis on those genes that cause the most common structural brain anomaly in humans called holoprosencephaly (HPE). This malformation of the brain can result from either environmental or genetic causes, and it is the aim of these investigations to determine the genes responsible for both normal and abnormal brain development through the study of patients with this disorder. Mutations in one such gene, Sonic Hedgehog, have been shown by us to be responsible for approximately one quarter of familial cases of HPE. Other genes either related to the hedgehog pathway or located at unrelated defined genetic loci may also contribute to HPE and are the subject of active investigation. We anticipate that many genes important for normal brain development will be identified in the search for genetic causes of HPE.

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(1) This research is open to all participants with a known or suspected diagnosis of HPE or related brain malformations. Since the range of severity of HPE is extensive, we accept cases compatible with a wide HPE spectrum of findings. All races and genders are known to be at risk for HPE, anywhere in the world. Nationality or place of origin are not specific barriers to participation, provided that a blood tissue sample can be safely sent by international FedEx (to be billed to our account).

(2) Direct blood relatives (typically parents, and occasionally siblings of affected individuals) of patients with HPE are also eligible to participate.

(3) Pregnant women with a fetus with imaging evidence of holoprosencephaly. Most pregnancies affected by holoprosencephaly do not survive to term; therefore, pregnant women will be included in the study. DNA obtained from pregnant women (amniocytes and blood) will be analyzed for genetic etiologies. This will allow for recurrence risk assessment and genetic counseling.


(1) Anyone unwilling to provide informed consent (for themselves as adults, or on behalf of their children as minors) or assent.

(2) Medical condition(s) or cognitive impairment are not in themselves reason for exclusion if in the judgement of the referring physician this would involve no more than minimal risk. We anticipate that children with mental handicaps would be included in the research population. We will make every effort to explain the study for the purpose of assent in a matter that the family feels is both age and developmentally appropriate for that child.

(3) We generally review a brief clinical description from the referring physician about a potential research subject to determine that the subject is appropriate to enter into the study. We reserve the right to exclude cases that are clearly not HPE or related to our direct research interests (e.g. HPE cases due to Trisomy 13 or 18 might not be considered directly related to current research). This almost never happens, and we would attempt to make referrals to a more appropriate investigator before a sample is sent to the NIH. Although not desirable, we will accept samples with a suspected diagnosis of HPE where this determination was made by the referring physician independent of any input from our HPE team. In such circumstances, we would likely verify by correspondence that a sample had been received and request further information.

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Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly

Perspectives on holoprosencephaly: Part I Epidemiology, genetics, and syndromology

Perspectives on holoprosencephaly: Part II Central nervous system, craniofacial anatomy, syndrome commentary, diagnostic approach, and experimental studies

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Principal Investigator

Referral Contact

For more information:

Benjamin D. Solomon, M.D.
National Human Genome Research Institute (NHGRI)
BG 10-CRC RM 3-2551
(301) 402-8824

Paul S. Kruszka Jr., M.D.
National Human Genome Research Institute (NHGRI)
BG 35 RM 1B-203
(301) 402-9654

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010

Clinical Trials Number:


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