Biallelic Variants in KIF17 Associated with Microphthalmia and Coloboma Spectrum

Abstract

Microphthalmia, anophthalmia, and coloboma (MAC) are a group of congenital eye anomalies that can affect one or both eyes. Patients can present one or a combination of these ocular abnormalities in the so called “MAC spectrum”. The KIF17 gene encodes the kinesin-like protein Kif17, a microtubule-based, ATP-dependent, motor protein that is pivotal for outer segment development and disc morphogenesis in different animal models, including mice and zebrafish. In this report, we describe a Sicilian family with two siblings affected with congenital coloboma, microphthalmia, and a mild delay of motor developmental milestones. Genomic DNA from the siblings and their unaffected parents was sequenced with a clinical exome that revealed compound heterozygous variants in the KIF17 gene (NM_020816.4: c.1255C > T (p.Arg419Trp); c.2554C > T (p.Arg852Cys)) segregating with the MAC spectrum phenotype of the two affected siblings. Variants were inherited from the healthy mother and father, are present at a very low-frequency in genomic population databases, and are predicted to be deleterious in silico. Our report indicates the potential co-segregation of these biallelic KIF17 variants with microphthalmia and coloboma, highlighting a potential conserved role of this gene in eye development across different species.

Ophthalmological Findings in Joubert Syndrome and Related Disorders

“…49 50 51 52 53 54 55 56 57 58 59 This led to a better understanding of the subcellular alterations underlying diseases, including several regulatory networks and genetic together with nongenetic factors. 60 61 62 63 64 65 66 67 68 69 70 Actually, there is still no effective treatment for JS patients, but our increasing understanding of the underlying genetic basis of various JS-related subtypes and the better genotype–phenotype correlations could lead to an advancement of the field in near future.…”

Epilepsy in Joubert Syndrome: A Still Few Explored Matter

“…[25][26][27][28][29][30][31][32][33][34][35][36][37] Importantly, genes that regulate cilium and/or neural development or that influence metabolic substrate or subcellular events have been revealed as causative for disorders which were previously neglected. [38][39][40][41][42][43][44][45][46][47] Our understanding of the processes associated with rare and/or multisystemic abnormalities will be pivotal for targeted treatments and the development of personalized pediatrics, according to several examples. [48][49][50][51][52][53][54][55][56][57] These observations might underlie the importance of an expanded metabolic screening especially in those patients with multiorgan involvement.…”

The Function and Role of the Cilium in the Development of Ciliopathies

“…[18][19][20][21][22][23][24][25][26] The molecular dissection of these conditions and the underlying genetic and/or immuno-mediated are interesting examples to explain the frequent intricated multisystemic, metabolic, and neurological abnormalities associated with a wide array of (both rare and common) pediatric disorders. [27][28][29][30][31][32][33][34][35][36]…”