Oculodentodigital Dysplasia Syndrome Research Articles

Novel GJA1/Cx43 Variant Associated With Oculo-Dento-Digital Dysplasia Syndrome: Clinical Phenotype and Cellular Mechanisms

Oculodentodigital dysplasia syndrome is associated with numerous pathogenic variants in GJA1, the gene encoding connexin43 gap junction protein. A novel in-frame deletion (p.Lys134del) was found in our clinic. The patient showed all the typical dysmorphic features of the syndrome. The functional consequences of this variant were also studied in an in vitro system. Cells expressed significantly less number of gap junction plaques with a great number of them retained intracellularly.

A case of oculodentodigital dysplasia syndrome with novel GJA1 gene mutation

To report a case of oculodentodigital dysplasia syndrome (ODDD) with a heterozygous mutation in GJA1 (connexin 43) gene. A 9-year-old girl visited our hospital complaining of visual disturbances. The patient had microphthalmia, a small nose with hypoplastic alae nasi, and syndactyly. Visual acuity with prescribed glasses improved to 0.5 (1.2) OU 2 months after the first visit. She was satisfied with the new glasses and the improvement in visual acuity. Genomic DNA was extracted from leukocytes of the patient's peripheral blood in accordance with standard procedures, after obtaining parental informed consent. We amplified GJA1 exon 2 from her genomic DNA by the PCR method, and sequenced the product using the dye terminator method. S5C (c. 13A > T), a novel mutation in exon 2 of GJA1, was found in the patient. The parents had no mutation of GJAI, nor was there any sign of abnormality in other family members. No similar mutation could be found in the 50 genotyped normal subjects in the control group. A novel GJA1 mutation was detected in a Japanese ODDD patient. Glaucoma complications associated with ODDD have already been reported. Careful long-term monitoring and treatment are also necessary.

Structural Assessment ofPITX2,FOXC1,CYP1B1, andGJA1Genes in Patients with Axenfeld-Rieger Syndrome with Developmental Glaucoma

Axenfeld-Rieger (AR) is an autosomal dominant disorder with phenotypic heterogeneity characterized by anterior segment dysgenesis, facial bone defects, and redundant periumbilical skin. The PITX2 gene, on chromosome 4q25, and the FOXC1 gene, on chromosome 6p25, have been implicated in the different phenotypes of the syndrome through mutational events. Recently, the CYP1B1 gene was found to be associated with Peters' anomaly, and the gene associated with oculodentodigital dysplasia syndrome, which presents some similarities with AR, was identified (connexin 43--GJA1 gene). The purpose of this study was to evaluate PITX2, FOXC1, CYP1B1, and GJA1 gene mutations in Brazilian families with AR. Eight unrelated patients affected by AR (all eight with glaucoma and three with systemic manifestations) and their families were ophthalmologically evaluated and their blood was collected for DNA extraction purposes. The coding regions of PITX2, FOXC1, CYP1B1, and GJA1 genes were completely evaluated through direct sequencing. The frequency of mutations in the FOXC1, GJA1, PITX2, and CYP1B1 genes in this study were 25%, 12.5%, 0% and 0%, respectively. In the FOXC1 gene, two GGC triplet insertions (GGC375ins and GGC447ins) defined as a polymorphism, and two new mutations--a deletion (718 to 719delCT) and a nonsense mutation (Trp152STOP)--were identified. One polymorphism (Ala253Val) was identified in the GJA1 gene in the same family presenting the Trp152STOP mutation in the FOXC1 gene. In this family harboring both structural alterations, two patients who carried the GJA1 (Ala253Val) and FOXC1 (Trp152STOP) mutations developed less severe glaucoma compared with family members presenting the FOXC1 (Trp152STOP) mutation alone. Two new structural alterations in the FOXC1 gene and a polymorphism in the GJA1 gene were first described in Brazilian patients with AR and developmental glaucoma. A polymorphism in the GJA1 gene (Ala253Val), for the first time identified in association with AR, raises the possibility of its participation as a modifier gene.

A Novel Mutation in the GJA1 Gene in a Family With Oculodentodigital Dysplasia

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. 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. 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. 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.

Delayed Gastric Emptying and Chronic Diarrhea in a Patient with Oculodentodigital Dysplasia Syndrome

Summary:A patient with oculodentodigital dysplasia (ODDD) syndrome was evaluated because of complaints of intermittent diarrhea of many years duration. Gastrointestinal manifestations have not been routinely described in patients with ODDD, which is a hereditary disorder characterized by abnormal eye findings, defective tooth enamel, various phalangeal aberrations, a distinctive facial appearance, and skeletal dysplasias. Steatorrhea was documented, but the usual methods for investigating this were thwarted ?? motility. A combined endoscopic‐fluoroscopic, guidewire‐directed intubation procedure was performed to permit study of the small bowel. Pancreatic function was normal, and culture of an aspirate from the jejunum revealed a mixed bacterial flora. Treatment for presumed small bowel bacterial overgrowth with antibiotics and a reduced fat diet brought relief of diarrheal symptoms and produced weight gain. The clinical approach to this particular patient and the relationship between the ODDD syndrome and the deseribed gastrointestinal anomalies are disecossed.

Delayed Gastric Emptying and Chronic Diarrhea in a Patient with Oculodentodigital Dysplasia Syndrome

A patient with oculodentodigital dysplasia (ODDD) syndrome was evaluated because of complaints of intermittent diarrhea of many years duration. Gastrointestinal manifestations have not been routinely described in patients with ODDD, which is a hereditary disorder characterized by abnormal eye findings, defective tooth enamel, various phalangeal aberrations, a distinctive facial appearance, and skeletal dysplasias. Steatorrhea was documented, but the usual methods for investigating this were thwarted by the patient's abnormal gastric anatomy and poor gastric motility. A combined endoscopic-fluoroscopic, guidewire-directed intubation procedure was performed to permit study of the small bowel. Pancreatic function was normal, and culture of an aspirate from the jejunum revealed a mixed bacterial flora. Treatment for presumed small bowel bacterial overgrowth with antibiotics and a reduced fat diet brought relief of diarrheal symptoms and produced weight gain. The clinical approach to this particular patient and the relationship between the ODDD syndrome and the described gastrointestinal anomalies are discussed.

Delayed Gastric Emptying and Chronic Diarrhea in a Patient with Oculodentodigital Dysplasia Syndrome

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