Missense and deletion mutations in GJA1 causing oculodentodigital dysplasia in two Indian families

Dwarakanathan, Abhilash; Bhat, Meenakshi; Gn, Sanjeeva; Shetty, Swathi

doi:10.1097/mcd.0000000000000094

Cited by 3 publications

(6 citation statements)

References 9 publications

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“…Second, neurological symptoms can be easily neglected if the diagnosis of ODDD is made by physicians with other specialties, especially when the symptoms are subtle. Moreover, there are cases that have not yet manifested neurological symptoms but have abnormal brain imaging findings [ 7 , 10 ]. Their neurological symptoms may become evident later in life.…”

Section: Discussionmentioning

confidence: 99%

“…The phenotypes of neurological manifestation may vary, as seen in Table 1 . Meanwhile, in those who underwent brain imaging, they exhibited similar abnormal imaging findings, such as symmetrical generalized white matter signal changes extending to the brainstem, atrophy of the brainstem and cerebellum, and calcification of the basal ganglia and dentate nucleus [ 4 , 7 , 10 ]. This finding may reflect the degeneration of the corticospinal tract and related regions caused by the aberrant signaling of gap junctions of astrocytes.…”

Section: Discussionmentioning

confidence: 99%

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Oculodentodigital Dysplasia Presenting as Spastic Paraparesis: The First Genetically Confirmed Korean Case and a Literature Review

Park

Ryu

Kim

et al. 2017

JMD

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Oculodentodigital dysplasia (ODDD) is a rare autosomal dominant inherited disease caused by mutations of the human gap junction alpha 1 gene, which encodes the protein Connexin-43. Patients with ODDD may present with neurological deficits with a typical pleiotropic combination of characteristic craniofacial, ophthalmological, phalangeal, and dental anomalies. In this report, we describe the first genetically confirmed Korean ODDD patient, who presented with spastic paraparesis. We will also review the neurological aspects of ODDD as reported in the literature.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Oculodentodigital Dysplasia Presenting as Spastic Paraparesis: The First Genetically Confirmed Korean Case and a Literature Review

Park

Ryu

Kim

et al. 2017

JMD

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“…Oculodentodigital dysplasia (ODDD, OMIM #164200) is a rare disorder mainly characterized by abnormal craniofacial, dental, ocular, and digital development. The autosomal dominant form has been the most frequently reported inheritance pattern, although a few cases of autosomal recessive inheritance have been described [1][2][3]. Craniofacial abnormalities may include microcephaly, prominent columella, and underdeveloped nasal alae [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…The gap junction protein alpha 1 (GJA1) gene codes for connexin-43, which is a protein that assists in the transmembrane transport of molecules through gap junctions, and mutations in the GJA1 may cause an alteration of the channel conduction properties [1][2][3]6]. We report a case of an 8-month-old female patient with an identified GJA1 mutation and common clinical features associated with ODDD.…”

Section: Introductionmentioning

confidence: 99%

Oculodentodigital Dysplasia: A Case Report and Major Review of the Eye and Ocular Adnexa Features of 295 Reported Cases

Kumar

Couser

Pandya

2020

Case Reports in Ophthalmological Medicine

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Oculodentodigital dysplasia (ODDD) is a rare genetic disorder associated with a characteristic craniofacial profile with variable dental, limb, eye, and ocular adnexa abnormalities. We performed an extensive literature review to highlight key eye features in patients with ODDD and report a new case of a female patient with a heterozygous missense GJA1 mutation (c.65G>A, p.G22E) and clinical features consistent with the condition. Our patient presented with multiple congenital anomalies including syndactyly, microphthalmia, microcornea, retrognathia, and a small nose with hypoplastic alae and prominent columella; in addition, an omphalocele defect was present, which has not been reported in previous cases. A systematic review of the published cases to date revealed 91 literature reports of 295 individuals with ODDD. There were 73 different GJA1 mutations associated with these cases, of which the most common were the following missense mutations: c.605G>A (p.R202H) (11%), c.389T>C (p.I130T) (10%), and c.119C>T (p.A40V) (10%). Mutations most commonly affect the extracellular-1 and cytoplasmic-1 domains of connexin-43 (gene product of GJA1), predominately manifesting in microphthalmia and microcornea. The syndrome appears with an approximately equal sex ratio. The most common eye features reported among all mutations were microcornea, microphthalmia, short palpebral fissures, and glaucoma.

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“…The major clinical features include (1) distinctive facial findings, including a thin nose with hypoplastic ala nasi, small anteverted nares, prominent columella, and microcephaly; (2) eye findings, such as microphthalmia and glaucoma; (3) syndactyly, typically digital malformation, including bilateral complete syndactyly of digits 4 and 5 (type III syndactyly), camptodactyly, and permanent joint flexion of the digits; (4) teeth anomalies and enamel hypoplasia; and (5) cardiac dysfunctions 2 – 4 . Some patients exhibit dysplastic ears and conductive hearing loss 5 , 6 . Various neurological symptoms, including dysarthria, spastic paraparesis, ataxia, and seizures, occur in ~30% of patients with ODDD 7 – 10 .…”

mentioning

confidence: 99%

Rare mosaic variant of GJA1 in a patient with a neurodevelopmental disorder

Shimomura,

Yanagishita,

Ishiguro

et al. 2024

Hum Genome Var

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GJA1 is the causative gene for oculodentodigital dysplasia (ODDD). A novel de novo GJA1 variant, NM 000165:c263C > T [p.P88L], was identified in a mosaic state in a patient with short stature, seizures, delayed myelination, mild hearing loss, and tooth enamel hypoplasia. Although the patient exhibited severe neurodevelopmental delay, other clinical features of ODDD, including limb anomalies, were mild. This may be due to differences in the mosaic ratios in different organs.

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Missense and deletion mutations in GJA1 causing oculodentodigital dysplasia in two Indian families

Cited by 3 publications

References 9 publications

Oculodentodigital Dysplasia Presenting as Spastic Paraparesis: The First Genetically Confirmed Korean Case and a Literature Review

Oculodentodigital Dysplasia Presenting as Spastic Paraparesis: The First Genetically Confirmed Korean Case and a Literature Review

Oculodentodigital Dysplasia: A Case Report and Major Review of the Eye and Ocular Adnexa Features of 295 Reported Cases

Rare mosaic variant of GJA1 in a patient with a neurodevelopmental disorder

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