Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia

William A. Paznekas, Simeon Boyd, Robert E. Shapiro, Otto Daniels, Bernd Wollnik, Catherine E. Keegan, Jeffrey W. Innis, Mary Beth Dinulos, Cathy Christian, Mark C. Hannibal, Ethylin Wang Jabs

Research output: Contribution to journalArticle

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Abstract

Gap junctions are assemblies of intercellular channels that regulate a variety of physiologic and developmental processes through the exchange of small ions and signaling molecules. These channels consist of connexin family proteins that allow for diversity of channel composition and conductance properties. The human connexin 43 gene, or GJA1, is located at human chromosome 6q22-q23 within the candidate region for the oculodentodigital dysplasia locus. This autosomal dominant syndrome presents with craniofacial (ocular, nasal, and dental) and limb dysmorphisms, spastic paraplegia, and neurodegeneration. Syndactyly type III and conductive deafness can occur in some cases, and cardiac abnormalities are observed in rare instances. We found mutations in the GJA1 gene in all 17 families with oculodentodigital dysplasia that we screened. Sixteen different missense mutations and one codon duplication were detected. These mutations may cause misassembly of channels or alter channel conduction properties. Expression patterns and phenotypic features of gja1 animal mutants, reported elsewhere, are compatible with the pleiotropic clinical presentation of oculodentodigital dysplasia.

Original languageEnglish (US)
Pages (from-to)408-418
Number of pages11
JournalAmerican Journal of Human Genetics
Volume72
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

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Connexin 43
Phenotype
Mutation
Connexins
Paraplegia
Ion Exchange
Gap Junctions
Human Chromosomes
Deafness
Missense Mutation
Nose
Codon
Genes
Tooth
Extremities
Oculodentodigital Dysplasia
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Paznekas, W. A., Boyd, S., Shapiro, R. E., Daniels, O., Wollnik, B., Keegan, C. E., ... Jabs, E. W. (2003). Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. American Journal of Human Genetics, 72(2), 408-418. https://doi.org/10.1086/346090

Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. / Paznekas, William A.; Boyd, Simeon; Shapiro, Robert E.; Daniels, Otto; Wollnik, Bernd; Keegan, Catherine E.; Innis, Jeffrey W.; Dinulos, Mary Beth; Christian, Cathy; Hannibal, Mark C.; Jabs, Ethylin Wang.

In: American Journal of Human Genetics, Vol. 72, No. 2, 01.02.2003, p. 408-418.

Research output: Contribution to journalArticle

Paznekas, WA, Boyd, S, Shapiro, RE, Daniels, O, Wollnik, B, Keegan, CE, Innis, JW, Dinulos, MB, Christian, C, Hannibal, MC & Jabs, EW 2003, 'Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia', American Journal of Human Genetics, vol. 72, no. 2, pp. 408-418. https://doi.org/10.1086/346090
Paznekas, William A. ; Boyd, Simeon ; Shapiro, Robert E. ; Daniels, Otto ; Wollnik, Bernd ; Keegan, Catherine E. ; Innis, Jeffrey W. ; Dinulos, Mary Beth ; Christian, Cathy ; Hannibal, Mark C. ; Jabs, Ethylin Wang. / Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. In: American Journal of Human Genetics. 2003 ; Vol. 72, No. 2. pp. 408-418.
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