CCDC88C, encoding coiled-coil domain containing 88C, is essential for cell communication during neural development. It is a component of non-canonical Wnt signaling and also contributes to ependymal cell planar polarity by inhibiting the non-canonical Wnt signaling pathway [2,3]. It is ubiquitously expressed and has functions in cell polarity and dendrite development in the nervous system [6].

In terms of diseases, CCDC88C variants are associated with multiple conditions. In epilepsy, two de novo and two biallelic CCDC88C variants were identified in focal epilepsy patients. De novo variants led to adult-onset epilepsy, while biallelic variants caused infant-onset epilepsy, and all patients responded well to anti-seizure medications [1]. In breast cancer, CCDC88C drives breast cancer cell motility in vitro and lung and liver metastasis in vivo, through promoting c-JUN-mediated CEMIP transcription [2]. CCDC88C pathogenic variants are also linked to congenital hydrocephalus, with brain lesions such as multifocal atresia-forking, periventricular neuronal heterotopias and choroid plexus hydrops in fetuses [3]. Additionally, it is associated with spinocerebellar ataxia (SCA40), and a novel mutation in it was found in a patient with late-onset ataxia, dysmetria and intention tremor [4,5]. A heterozygous mutation in CCDC88C likely caused early-onset pure hereditary spastic paraplegia in a case report [6].

In conclusion, CCDC88C plays a crucial role in neural development, cell communication and is involved in multiple disease conditions including epilepsy, breast cancer, congenital hydrocephalus, spinocerebellar ataxia and early-onset pure hereditary spastic paraplegia. Understanding its function through studies on its variants helps in comprehending the disease mechanisms, which may provide potential directions for disease treatment and prevention.

References:

1. Chen, Yu-Jie, Wang, Wen-Jie, Zou, Dong-Fang, Li, Bin, Chen, Yong-Jun. 2024. CCDC88C variants are associated with focal epilepsy and genotype-phenotype correlation. In Clinical genetics, 105, 397-405. doi:10.1111/cge.14476. https://pubmed.ncbi.nlm.nih.gov/38173219/

2. Deng, Boya, Zhang, Siyang, Zhou, Yingying, Li, Ailin, Miao, Yuan. 2024. CCDC88C, an O-GalNAc glycosylation substrate of GALNT6, drives breast cancer metastasis by promoting c-JUN-mediated CEMIP transcription. In Cancer cell international, 24, 237. doi:10.1186/s12935-024-03413-2. https://pubmed.ncbi.nlm.nih.gov/38971758/

3. Marguet, Florent, Vezain, Myriam, Marcorelles, Pascale, Laquerriere, Annie, Saugier-Veber, Pascale. 2021. Neuropathological hallmarks of fetal hydrocephalus linked to CCDC88C pathogenic variants. In Acta neuropathologica communications, 9, 104. doi:10.1186/s40478-021-01207-5. https://pubmed.ncbi.nlm.nih.gov/34092257/

4. Chai, Senmao, Liu, Deyang, Liu, Yajing, Sang, Ming. 2023. A Novel c.3636-4 A>G Mutation in the CCDC88C Plays a Causative Role in Familial Spinocerebellar Ataxia. In Human heredity, 88, 91-97. doi:10.1159/000534692. https://pubmed.ncbi.nlm.nih.gov/37899026/

5. Boros, Fanni Annamária, Szpisjak, László, Bozó, Renáta, Széll, Márta, Ádám, Éva. 2023. Spinocerebellar Ataxia in a Hungarian Female Patient with a Novel Variant of Unknown Significance in the CCDC88C Gene. In International journal of molecular sciences, 24, . doi:10.3390/ijms24032617. https://pubmed.ncbi.nlm.nih.gov/36768938/

6. Yahia, Ashraf, Chen, Zhefan Stephen, Ahmed, Ammar E, Chan, Ho Yin Edwin, Stevanin, Giovanni. 2021. A heterozygous mutation in the CCDC88C gene likely causes early-onset pure hereditary spastic paraplegia: a case report. In BMC neurology, 21, 78. doi:10.1186/s12883-021-02113-y. https://pubmed.ncbi.nlm.nih.gov/33602173/