Colobomatous macrophthalmia with microcornea syndrome maps to the 2p23‐p16 region

Abstract

Colobomatous macrophthalmia with microcornea syndrome (OMIM 602499) is a rare, autosomal dominant malformation characterized by microcornea, uveal coloboma, axial enlargement of the globe, and myopia. Using what is currently the largest described pedigree and candidate localization approach, we first excluded the candidate genes PAX2, PAX3, PAX6, and PAX9. Subsequently, the chromosome 14q24 region containing the CHX10, SIX1, and SIX4 genes were also excluded. Positive LOD scores were obtained with the DNA markers selected from the 2p23-p16 region. A maximum pairwise LOD score of 3.61 (Theta = 0) was noted with the DNA marker D2S1788. Haplotype analysis positioned the locus between DNA markers D2S2263 and D2S1352 within a 22 Mb physical interval. This region contains major candidate genes, such as SIX2, SIX3, and CYP1B1; however, mutation analysis did not identify a causative mutation in these genes. Macrophthalmia, colobomatous, with microcornea (MACOM) is proposed as the gene symbol for this malformation linked to 2p23-p16.

CRIM1 haploinsufficiency causes defects in eye development in human and mouse

“…In the same family, Elcioglu et al performed linkage analysis and identified the maximum possible LOD score of 3.61 in a candidate region on chromosome 2. Consistent with the large number of family members included in the linkage analysis, the probability of producing an LOD score of 3.61 by chance is very low (P ≤ 0.0001) (6). We therefore focused the search for the causative gene on this region, but we could not identify any candidate mutation after the initial analysis.…”

Inherited eye diseases in Turkey: Current approaches and future directions

“…The number of animal studies investigating mechanisms of inherited eye disorders was also limited (Yaylacioglu Tuncay & Dincer, 2019). There have been relatively fewer studies investigating the genotype–phenotype correlations in inherited eye diseases from Turkey (Bardak et al, 2016; Ergun, Akay, Ergun, & Perçin, 2017; Karti et al, 2017; Semerci et al, 2014; Yaylacioglu Tuncay et al, 2016), and the most of these publications were accomplished by international collaborations (Bagiyeva et al, 2007; Elcioglu et al, 2007; Holt et al, 2017; Ozgul et al, 2004; Yamada et al, 2004) or by including Turkish patients living abroad (Angius et al, 2018; Iftikhar et al, 2019; Pach, Kohl, Gekeler, & Zobor, 2013). The dataset should grow about the genotypes of patients living in Turkey.…”