A Study of the Genetic Analysis of Brain Disorders

NCT00645645 | Completed

• 2 other identifiers: 98024998-HG-0249
• Study Type: observational
• Target: 5,735
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Holoprosencephaly

Keywords

Holoprosencephaly; Agenesis of Corpus; Callosum; Genetic Tests

Outcome Measures

Primary Outcomes (1)

• natural history

  The objectives of this study are primarily to increase our understanding of the genetic causes of brain malformations.

  lifetime/ongoing

Study Arms (1)

holoprosencephaly (HPE)

individuals with overt or subtle clinical findings consistent with the HPE spectrum are eligible to participate

Eligibility Criteria

• Age: 1 Month+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with HPE.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Belloni E, Muenke M, Roessler E, Traverso G, Siegel-Bartelt J, Frumkin A, Mitchell HF, Donis-Keller H, Helms C, Hing AV, Heng HH, Koop B, Martindale D, Rommens JM, Tsui LC, Scherer SW. Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly. Nat Genet. 1996 Nov;14(3):353-6. doi: 10.1038/ng1196-353.

  PMID: 8896571 BACKGROUND

• Cohen MM Jr. Perspectives on holoprosencephaly: Part I. Epidemiology, genetics, and syndromology. Teratology. 1989 Sep;40(3):211-35. doi: 10.1002/tera.1420400304.

  PMID: 2688166 BACKGROUND

• Cohen MM Jr, Sulik KK. Perspectives on holoprosencephaly: Part II. Central nervous system, craniofacial anatomy, syndrome commentary, diagnostic approach, and experimental studies. J Craniofac Genet Dev Biol. 1992 Oct-Dec;12(4):196-244.

  PMID: 1494025 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Holoprosencephaly

Condition Hierarchy (Ancestors)

Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Agenesis of Corpus Callosum; Nervous System Malformations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Officials

• Benjamin D Solomon, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2008
• First Posted: March 28, 2008
• Study Start: June 1, 2008
• Primary Completion: January 19, 2021
• Study Completion: January 19, 2021
• Last Updated: December 14, 2021

Record last verified: 2021-12

Locations

US (1)