Prevention of childhood blindness in the concept of congenital cataracts was among the main objectives in vision 2020 [11]. So, it is claimed that this growing and high prevalence pediatric disorder should be seriously managed [10]. Investigations in the area of molecular etiology in inherited cataracts demonstrated that underlying gene abnormalities of this disorder could be divided into 4 groups, including crystallin mutations, lens membrane protein mutations, mutations of lens cytoskeletal elements, and the other remaining mutations [11]. However, most of them are included in the crystallin genes group [11].
Hence, in this study, we examined the probable disease-causing mutation in an 8-month-old affected boy, referred to medical genetics for congenital cataract and visual impairment.
In addition, this family reported a history of congenital cataracts in siblings of parents. In contrast, parents were healthy individuals without a history of eye disorder. The WES and Sanger sequencing were used to identify the impaired gene in this family, and a homozygous pathologic FYCO1 (c.1387 G > T; p.G463X) mutation associated with AR infantile cataract was detected in the patient (8-months-old boy), followed by heterozygous mutations in his consanguine parents. This substitution leads to premature termination of the FYCO1 protein by converting the glycine at position 463 to a stop codon, can create major problem in the FYCO1 protein.
The FYCO1 gene, which is located on chromosome 3 (3p21.31), consists of 18 exons (NM_024513.4) and plays a crucial role in lens progression and transparency in humans [7]. In addition, it has been declared that FYCO1 is an autophagy adaptor protein and a part of the PI(3)P-binding protein family [9]. Previous studies revealed that the AR form of CC could be a consequence of FYCO1 gene mutations. In this regard, Chen et al., in their publication, showed causative nonsense and frameshift FYCO1 mutations in 13 unrelated families with CC. Furthermore, Hira Iqbal et al. evaluating pathogenic genomic defects in three consanguineous families, introduced two novels and one known mutation in the FYCO1 gene and concluded that mutations in FYCO1 accounted for approximately 15% of total cases of autosomal recessive CC [9]. Subsequently, Raffi Aprahamian et al. reported a novel homozygous pathogenic variant (c.2365 C > T) in exon 8 of the FYCO1 gene in a Lebanese infant [12]. In line with these findings, Nikolay A. Barashkov et al. also investigated the genetic defect of CC in the Turkic-speaking Yakut population using WES and presented a novel homozygous c.1621 C > T mutation that resulted in a premature stop codon. More assessment showed that this mutation existed in 86% of CC-affected patients in this population and may be due to the founder effect [5].
Altogether, FYCO1 gene mutations in inherited or sporadic states have been reported from various regions worldwide but in a high prevalence from Pakistan. The affected patient in our study has Iraqi descent, which in consanguineous marriage is common, so they are more susceptible to transfer abnormal genes or inherited disorders. Since identifying the genetic etiology of CC is a basic milestone of clear insights into underlying pathogenesis pathways and recognizing susceptible populations, it can help to reduce affected cases by prenatal molecular diagnosis, especially in consanguine parents or even genetic consulting before marriage [11].
Finally, it seems that this point of detected mutation is a rare mutational hotspot point that carried in patient ancestors. The obtained results and family history suggest considering this gene mutation in the genetic test platform of AR cataract cases.
