Genetic and Functional Analysis of Craniometaphyseal Dysplasia (CMD) (CMD)

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ClinicalTrials.gov Identifier: NCT01630460

Recruitment Status : Recruiting

First Posted : June 28, 2012

Last Update Posted : December 14, 2020

See Contacts and Locations

Sponsor:

Information provided by (Responsible Party):

Ernst Reichenberger, UConn Health

Study Description

Brief Summary:

CMD can be inherited in an autosomal dominant or recessive trait. CMD may also be caused by de novo mutations. The goal of this study is to identify genes and regulatory elements on chromosomes that are the cause for CMD. The investigators also study blood samples and tissue samples from patients to learn about the processes that lead to this disorder. The investigators long-term goal is to find mechanisms to slow down bone deposition in CMD patients.

Condition or disease
Craniometaphyseal Dysplasia

Detailed Description:

CMD is a very rare bone disorder that affects mostly bones of the head (=cranial bones) but also long (=tubular) bones. Therefore, CMD has been added to the class of craniotubular bone disorders. There are a number of disorders in this group and sometimes they are difficult to distinguish. Typical signs for CMD are the lifelong bone deposition in bones of the face and head (=progressive craniofacial hyperostosis) and the widening of the ends of long bones (=metaphyseal flaring). Typical facial characteristics are wide-set eyes and a prominent jaw (=mandible). CMD is sometimes diagnosed in infants. The best way to confirm diagnosis is by molecular genetics.

Study Design

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Study Type :	Observational
Estimated Enrollment :	600 participants
Observational Model:	Case-Control
Time Perspective:	Prospective
Official Title:	Identification of Mutations That Lead to Craniometaphyseal Dysplasia in Families and Isolated Cases and Studies of Cellular and Molecular Mechanisms
Study Start Date :	April 2009
Estimated Primary Completion Date :	December 2025
Estimated Study Completion Date :	December 2025

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Nager syndrome Craniometaphyseal dysplasia

Genetic and Rare Diseases Information Center resources: Crouzon Syndrome

U.S. FDA Resources

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

Identification of genetic elements [ Time Frame: at time of identification ]
The goal is to identify relevant genes or genetic elements that cause the disease or contribute to the disease progression and severity.

Biospecimen Retention: Samples With DNA

Saliva, blood, bone tissue

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Individuals with diagnosed CMD

Criteria

Inclusion Criteria:

CMD; unaffected individuals only if part of a participating CMD family

Exclusion Criteria:

No CMD; unaffected individuals only as part of a participating CMD family

Contacts and Locations

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): NCT01630460

Contacts

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Contact: Ernst J Reichenberger, PhD	860-679-2062	reichenberger@uchc.edu

Locations

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United States, Connecticut
University of Connecticut Health Center	Recruiting
Farmington, Connecticut, United States, 06030
Contact: Ernst J Reichenberger, PhD 860-679-2062 reichenberger@uchc.edu

Sponsors and Collaborators

UConn Health

Investigators

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Principal Investigator:	Ernst J Reichenberger, PhD	UConn Health

More Information

Additional Information:

study website This link exits the ClinicalTrials.gov site

Publications of Results:

Dutra EH, Chen IP, McGregor TL, Ranells JD, Reichenberger EJ. Two novel large ANKH deletion mutations in sporadic cases with craniometaphyseal dysplasia. Clin Genet. 2012 Jan;81(1):93-5. doi: 10.1111/j.1399-0004.2011.01700.x.

Chen IP, Wang L, Jiang X, Aguila HL, Reichenberger EJ. A Phe377del mutation in ANK leads to impaired osteoblastogenesis and osteoclastogenesis in a mouse model for craniometaphyseal dysplasia (CMD). Hum Mol Genet. 2011 Mar 1;20(5):948-61. doi: 10.1093/hmg/ddq541. Epub 2010 Dec 13.

Chen IP, Wang CJ, Strecker S, Koczon-Jaremko B, Boskey A, Reichenberger EJ. Introduction of a Phe377del mutation in ANK creates a mouse model for craniometaphyseal dysplasia. J Bone Miner Res. 2009 Jul;24(7):1206-15. doi: 10.1359/jbmr.090218.

Reichenberger E, Chen IP. Craniometaphyseal Dysplasia, Autosomal Dominant. 2007 Aug 27 [updated 2020 Jun 11]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1461/

Reichenberger E, Tiziani V, Watanabe S, Park L, Ueki Y, Santanna C, Baur ST, Shiang R, Grange DK, Beighton P, Gardner J, Hamersma H, Sellars S, Ramesar R, Lidral AC, Sommer A, Raposo do Amaral CM, Gorlin RJ, Mulliken JB, Olsen BR. Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK. Am J Hum Genet. 2001 Jun;68(6):1321-6. Epub 2001 Apr 16.

Hu Y, Chen IP, de Almeida S, Tiziani V, Do Amaral CM, Gowrishankar K, Passos-Bueno MR, Reichenberger EJ. A novel autosomal recessive GJA1 missense mutation linked to Craniometaphyseal dysplasia. PLoS One. 2013 Aug 12;8(8):e73576. doi: 10.1371/journal.pone.0073576. eCollection 2013.

Dutra EH, Chen IP, Reichenberger EJ. Dental abnormalities in a mouse model for craniometaphyseal dysplasia. J Dent Res. 2013 Feb;92(2):173-9. doi: 10.1177/0022034512468157. Epub 2012 Nov 15.

Chen IP, Tadinada A, Dutra EH, Utreja A, Uribe F, Reichenberger EJ. Dental Anomalies Associated with Craniometaphyseal Dysplasia. J Dent Res. 2014 Jun;93(6):553-8. doi: 10.1177/0022034514529304. Epub 2014 Mar 24.

Chen IP, Luxmi R, Kanaujiya J, Hao Z, Reichenberger EJ. Craniometaphyseal Dysplasia Mutations in ANKH Negatively Affect Human Induced Pluripotent Stem Cell Differentiation into Osteoclasts. Stem Cell Reports. 2017 Nov 14;9(5):1369-1376. doi: 10.1016/j.stemcr.2017.09.016. Epub 2017 Oct 19.

Kanaujiya J, Bastow E, Luxmi R, Hao Z, Zattas D, Hochstrasser M, Reichenberger EJ, Chen IP. Rapid degradation of progressive ankylosis protein (ANKH) in craniometaphyseal dysplasia. Sci Rep. 2018 Oct 24;8(1):15710. doi: 10.1038/s41598-018-34157-5.

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Responsible Party:	Ernst Reichenberger, Assoc. Prof., UConn Health
ClinicalTrials.gov Identifier:	NCT01630460
Other Study ID Numbers:	UCHC03-008CMD
First Posted:	June 28, 2012 Key Record Dates
Last Update Posted:	December 14, 2020
Last Verified:	December 2020

Keywords provided by Ernst Reichenberger, UConn Health:


Craniometaphyseal dysplasia bone hyperostosis osteoblast osteoclast

Additional relevant MeSH terms:

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Hypertelorism Hyperostosis Hyperplasia Pathologic Processes Craniofacial Dysostosis Dysostoses	Bone Diseases, Developmental Bone Diseases Musculoskeletal Diseases Craniofacial Abnormalities Musculoskeletal Abnormalities Congenital Abnormalities

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