Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia.
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.
Paznekas
William A
WA
Department of Pediatrics, Center for Craniofacial Development and Disorders, McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Boyadjiev
Simeon A
SA
Shapiro
Robert E
RE
Daniels
Otto
O
Wollnik
Bernd
B
Keegan
Catherine E
CE
Innis
Jeffrey W
JW
Dinulos
Mary Beth
MB
Christian
Cathy
C
Hannibal
Mark C
MC
Jabs
Ethylin Wang
EW
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002896:Chromosomes, Human, Pair 6; D018031:Connexin 43 / Q000235:genetics*; D017124:Conserved Sequence; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000473:pathology*; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017880:Limb Deformities, Congenital / Q000235:genetics / Q000473:pathology*; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D018126:Odontodysplasia / Q000235:genetics* / Q000473:pathology*; D017386:Sequence Homology, Amino Acid
D018031:Connexin 43