A novel mutation in the GJA1 gene in a family with oculodentodigital dysplasia.

Arch Ophthalmol. 2005 Oct;123(10):1422-6

Authors: Vasconcellos JP, Melo MB, Schimiti RB, Bressanim NC, Costa FF, Costa VP

OBJECTIVES: To describe a Brazilian family with oculodentodigital dysplasia (ODDD) and to screen for mutations in the gap junction protein alpha 1 (GJA1) gene in this family. METHODS: Twelve members of a 3-generation family with ODDD underwent screening for mutations of the GJA1 gene and a comprehensive ophthalmic examination. We defined ODDD on the basis of clinical characteristics described in this syndrome (microdontia, caries, enamel hypoplasia, thin nose, and syndactyly) and eye abnormalities such as microphthalmos, iris atrophy, and glaucoma. Direct sequencing of the GJA1 gene was performed using DNA collected from peripheral blood. A control group of 60 healthy individuals underwent evaluation by means of enzyme digestion. RESULTS: Among the 8 members of this family who were characterized as having ODDD, 2 showed chronic angle-closure glaucoma, and 1 had open-angle glaucoma. A new mutation in the GJA1 gene was identified, consisting of a change from proline to histidine at codon 59. This mutation segregated through members with the ODDD phenotype. Analysis of the control group by means of restriction fragment length polymorphism (MvaI enzyme) did not disclose this mutation. CONCLUSION: Our results demonstrate a new mutation (P59H) in the GJ1A gene, identified in a family with ODDD syndrome.Clinical Relevance The presence of different forms of glaucoma in families with ODDD may indicate a new mutation in the GJA1 gene.

PMID: 16219735 [PubMed - indexed for MEDLINE]

Rabson-Mendenhall syndrome.

Indian J Med Sci. 2005 Feb;59(2):70-3

Authors: Kumar S, Tullu MS, Muranjan MN, Kamat JR

Rabson-Mendenhall syndrome is characterized by growth retardation, dysmorphisms, lack of subcutaneous fat, acanthosis nigricans, enlarged genitalia, hirsutism, premature and dysplastic dentition, coarse facial features, paradoxical fasting hypoglycemia and post-prandial hyperglycemia, extreme hyperinsulinemia and pineal hyperplasia. We describe a six-month-old female child with physical features suggestive of the Rabson-Mendenhall syndrome. The child also had medullary nephrocalcinosis.

PMID: 15738613 [PubMed - indexed for MEDLINE]

Segmental odontomaxillary dysplasia.

Med Oral. 2004 Mar-Apr;9(2):181, 181

Authors: Gavalda C

PMID: 14990887 [PubMed - indexed for MEDLINE]

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

Am J Hum Genet. 2003 Feb;72(2):408-18

Authors: Paznekas WA, Boyadjiev SA, Shapiro RE, Daniels O, Wollnik B, Keegan CE, Innis JW, Dinulos MB, Christian C, Hannibal MC, Jabs EW

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.

PMID: 12457340 [PubMed - indexed for MEDLINE]

Structural, ultrastructural, microradiographic, and electron-probe studies of an unusual case of regional odontodysplasia.

J Dent Res. 1982 Sep;61(9):1056-62

Authors: Kerebel B, Kerebel LM

Structural, ultrastructural, microradiographic, and electron microprobe studies of an unusual case of odontodysplasia were performed. Two cusps were absent from one molar. Normal prismatic enamel and mantle dentin were present on the two others. The dentinal mass resembled osteodentin. The mineral content of enamel and dentin was decreased compared to that of the controls.

PMID: 6302148 [PubMed - indexed for MEDLINE]