Microcornea, iris and choroidal coloboma, and global developmental delay caused by TENM3 pathogenic variants in a
Youfeng Zhou1, Ke Xu2, Weiyue Gu2
1Department of Pediatrics, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Background:
Biallelic TENM3 pathogenic variants cause isolated or syndromic microphthalmia. Syndromic microphthalmia 15 (MCOPS15) is characterized by microphthalmia, coloboma, and developmental delay. Currently, only four cases of MCOPS15 have been reported and the clinical features varied among the patients indicating potential broad phenotypic spectrum.
Methods:
The present case was a 6-month-old male at diagnosis. The patient exhibited long philtrum, large ears, bilateral ptosis, and nystagmus. Ophthalmic tests showed that he had microcornea, iris and choroidal coloboma. The patient presented with global developmental delay (GDD). Trio-whole exome sequencing and genome copy number sequencing were conducted to explore the disease-causing mutations.
Results:
Exome sequencing and genome copy number sequencing showed the presence of L1471F and E661G compound mutations in TENM3, which were inherited from the mother and father, respectively. Sanger sequencing was conducted to verify association of the mutations with the disease in the present family.
Conclusion:
Two TENM3 variants were identified in a patient with Syndromic microphthalmia 15 in the present study. However, further studies should be conducted to explore the pathogenicity of the variants.
Insights
Genetic variants in TENM3 cause Syndromic Microphthalmia 15 (MCOPS15), a rare condition. This study identified compound mutations in TENM3, expanding the understanding of MCOPS15.
Area of Science:
- Genetics
- Ophthalmology
- Developmental Biology
Background:
- Biallelic pathogenic variants in TENM3 gene are associated with microphthalmia.
- Syndromic Microphthalmia 15 (MCOPS15) is characterized by microphthalmia, coloboma, and developmental delay.
- Limited cases reported suggest a broad phenotypic spectrum for MCOPS15.
Observation:
- A 6-month-old male presented with microphthalmia, coloboma, ptosis, nystagmus, and global developmental delay (GDD).
- Clinical features included long philtrum, large ears, microcornea, and iris/choroidal coloboma.
- Trio-whole exome and genome copy number sequencing were performed.
Findings:
- Compound heterozygous mutations (L1471F and E661G) in the TENM3 gene were identified.
- These TENM3 variants were inherited from the patient's parents.
- Sanger sequencing confirmed the association of these mutations within the family.
Implications:
- Identifies novel compound mutations in TENM3 associated with MCOPS15.
- Highlights the role of TENM3 in ocular and neurological development.
- Further research is needed to fully elucidate the pathogenicity of these TENM3 variants.
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