Homozygous LAMC3 mutation links to structural and functional changes in visual attention networks

Abstract

The occipital lobe contains a substantial part of the neural machinery involved in visual perception. Mutations in the LAMC3 gene have recently been shown to cause complex bilateral occipital cortical gyration abnormalities. However, to what extent these structural changes impact visual behavior is not known. We recorded responses for two screening test batteries targeting visual function (Leuven - Perceptual Organization Screening Test, Cortical Vision Screening Test) and measured eye fixation performance in a visual attention experiment from a patient with homozygous LAMC3 gene mutation. Using voxel-based morphometry (VBM) we quantitatively assessed the extent of structural changes brought on by the genetic mutation by comparing mean cortical curvature, cortical thickness, and gray matter volume in 34 cortical areas between patient and an age-, sex-, and education-matched control group. Anatomical connectivity between these cortical areas was investigated by a structural covariance analysis. Visual screening-, and behavioral results revealed that the patient's impairments were predominantly in visuo-spatial attention. Consistent with this, VBM and structural connectivity results revealed significant structural changes in cortical regions subserving attentional functions. We conclude that the LAMC3 gene mutation affects cortical areas beyond the occipital lobe and primarily those visual functions that involve heavily distributed networks - such as visuo-spatial attention.

Identification of Therapeutic and Prognostic Biomarkers of Lamin C (LAMC) Family Members in Head and Neck Squamous Cell Carcinoma

“…In skin, LAMC3 was expressed in the basement membrane at the dermal-epidermal junction of the nerve penetration points [ 17 ]. Some studies have demonstrated that LAMC3 mutation is linked to changes in the structure and function of the visual attention network [ 44 ], which modulates astrocyte migration and angiogenesis by modulating the activation of retinal microglia. LAMC3 was essential for retinal layered photoreceptor organization, and synaptic stability [ 45 ].…”

A novel splice variant expands the LAMC3‐associated cortical phenotype to frontal only polymicrogyria and adult‐onset epilepsy

“…In accordance with this wider—though weaker—expression also in the frontal cortex, one individual with generalized polymicrogyria also extending to parietal and frontal lobes was reported (Zambonin et al, 2018). Of note, in one of the initially reported individuals (Barak et al, 2011), voxel‐based morphometry and structural connectivity analysis later also indicated impaired cortical areas beyond the occipital lobes (Urgen et al, 2019). While the classification of cortical malformation as polymicrogyria in the herewith reported individual fits to the previous reports, she is the only one with spared occipital lobes and polymicrogyria being present in the frontal lobes only.…”

Hypomethylation inFASTKD1detected in the association betweenin uterotobacco exposure and conduct problem in a New Zealand longitudinal study

“…LAMC3 has diverse roles in cell migration, apoptosis and adhesion, and variants within this gene have been found to contribute to cortical malformations [50–52]. It has been reported that individuals with these variants also have specific behavioural outcomes, e.g., impairments in endogenous attentional processes [51], which collectively suggests that these data may have biological relevance to the CP phenotype.…”