Genetic and Functional Analysis of Craniometaphyseal Dysplasia (CMD)

NCT01630460 | Recruiting

• 1 other identifier: UCHC03-008CMD
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 1

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.

Conditions

Craniometaphyseal Dysplasia

Keywords

Craniometaphyseal dysplasia; bone; hyperostosis; osteoblast; osteoclast

Outcome Measures

Primary Outcomes (1)

• Identification of genetic elements

  The goal is to identify relevant genes or genetic elements that cause the disease or contribute to the disease progression and severity.

  at time of identification

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with diagnosed CMD

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• UConn Health: lead

Study Sites (1)

University of Connecticut Health Center

Farmington, Connecticut, 06030, United States

RECRUITING

Related Publications (11)

• 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. No abstract available.

  PMID: 22150416 RESULT

• 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.

  PMID: 21149338 RESULT

• 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.

  PMID: 19257826 RESULT

• Reichenberger E, Chen IP. Autosomal Dominant Craniometaphyseal Dysplasia. 2007 Aug 27 [updated 2025 Aug 14]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1461/

  PMID: 20301634 RESULT

• 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. doi: 10.1086/320612. Epub 2001 Apr 16.

  PMID: 11326338 RESULT

• 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.

  PMID: 23951358 RESULT

• 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.

  PMID: 23160629 RESULT

• 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.

  PMID: 24663682 RESULT

• 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.

  PMID: 29056330 RESULT

• 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.

  PMID: 30356088 RESULT

• Fujii Y, Kozak E, Dutra E, Varadi A, Reichenberger EJ, Chen IP. Restriction of Dietary Phosphate Ameliorates Skeletal Abnormalities in a Mouse Model for Craniometaphyseal Dysplasia. J Bone Miner Res. 2020 Oct;35(10):2070-2081. doi: 10.1002/jbmr.4110. Epub 2020 Jul 12.

  PMID: 33463757 RESULT

Related Links

• study website

Biospecimen

Retention: SAMPLES WITH DNA

Saliva, blood, bone tissue

MeSH Terms

Conditions

Schwartz-Lelek syndrome; Hyperostosis

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases

Study Officials

• Ernst J Reichenberger, PhD

  UConn Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ernst J Reichenberger, PhD

CONTACT

860-679-2062; reichenberger@uchc.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: June 25, 2012
• First Posted: June 28, 2012
• Study Start: April 1, 2009
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (1)