TUBGCP4 - associated microcephaly and chorioretinopathy
Mariana Matioli Da Palma1, Fabiana Louise Motta1, Guilherme Eiichi Da Silva Takitani1
1Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil.
Abstract:
Background Microcephaly and chorioretinopathy (MCCRP) is a rare neuro-ophthalmologic disorder that causes microcephaly and chorioretinopathy. In a recessive inheritance pattern, there are three types: MCCRP1; MCCRP2 and MCCRP3. MCCRP3 results from pathogenic variants in the tubulin-gamma complex-associated protein 4 (TUBGCP4) gene.Materials and Methods This is a case report of a patient with a molecular diagnosis defined by mutations in the TUBGCP4 gene. Segregation analyses were carried out.Results The molecular investigation found two heterozygous variants c.1380 G > A (p.Trp460*) a novel nonsense variant, and c.1746 G > T (p Leu582=) a synonymous variant in TUBGCP4. The clinical phenotype was characterized by microcephaly, microphthalmia, chorioretinopathy, a punched-out retinal appearance, dysmorphic facial features, decreased visual acuity, and learning difficulties. The clinical features were similar to those described previously in children with MCCRP3. The proband also had additional features including centripetal obesity, stretch marks, acanthosis nigricans, scoliosis, and hypercholesterolemia. These other features could be part of a ciliopathy syndrome.Conclusions MCCRP2 caused by pathogenic variants in PLK4 is well established as a ciliopathy disease. The role of TUBGCP4 is not well established in the cilium physiology. MCCRP3 may be part of the ciliopathy spectrum.
Insights
Microcephaly and chorioretinopathy type 3 (MCCRP3), caused by TUBGCP4 gene variants, presents with microcephaly and vision loss. This rare disorder may be linked to ciliopathy, expanding the known spectrum of these genetic conditions.
Area of Science:
- Genetics
- Ophthalmology
- Neurology
Background:
- Microcephaly and chorioretinopathy (MCCRP) is a rare, recessively inherited neuro-ophthalmologic disorder.
- MCCRP presents in three types: MCCRP1, MCCRP2, and MCCRP3.
- MCCRP3 is specifically linked to pathogenic variants in the tubulin-gamma complex-associated protein 4 (TUBGCP4) gene.
Observation:
- A case report details a patient with MCCRP3 diagnosed through molecular investigation of the TUBGCP4 gene.
- The patient exhibited microcephaly, microphthalmia, chorioretinopathy with a punched-out retinal appearance, dysmorphic facial features, reduced visual acuity, and learning difficulties.
- Additional features included obesity, stretch marks, acanthosis nigricans, scoliosis, and hypercholesterolemia, suggesting a potential ciliopathy link.
Findings:
- Two heterozygous variants in TUBGCP4 were identified: a novel nonsense variant (c.1380 G>A; p.Trp460*) and a synonymous variant (c.1746 G>T; p Leu582=).
- The patient's clinical presentation aligns with previously described MCCRP3 cases.
- The additional observed features suggest MCCRP3 might be associated with ciliopathies.
Implications:
- This study contributes to understanding the genetic basis of MCCRP3 and the role of TUBGCP4.
- The findings suggest that MCCRP3 could be part of a broader ciliopathy spectrum, similar to MCCRP2.
- Further research is needed to clarify the precise role of TUBGCP4 in cilium physiology and its connection to ciliopathies.
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