Background

Intellectual disability (ID) is a hallmark of many rare disorders that are highly heterogeneous and complex. A large number of specific genes are involved in development of this heterogeneity, and each of these genes is only found in a small number of patients. This weakens the definition of the predominant genotype and the phenotypic characteristics associated with that gene. Autosomal recessive ID type 66 (OMIM # 618221) is one of these very rare diseases created by defects in C12orf4 gene.

Methods

The researchers in the current study included two patients from an Iranian family with initial diagnosis of non-syndromic ID to identify the possible genetic cause(s), and whole-exome sequencing (WES) was performed for the proband. The obtained variant was confirmed by Sanger sequencing and co-segregated in the family.

Result

The patients carried a novel pathogenic splicing variant called c.1441-1G>A in exon 12 of C12orf4 gene (NM_001304811). They predominantly manifested ID, behavioral problems, speech impairment, and dysmorphic facial features, some of which had not been reported in previous studies.

Conclusion

A novel pathogenic splicing variant was identified named c.1441-1G>A in C12orf4 gene. So far, only seven families have been reported with defects in this gene. Previous studies have not highlighted the exact clinical manifestations of these patients, thus, this study could contribute to better delineation of the genotype-phenotype correlation and interpretation of very rare variants of the gene.