Variants in LAMC3 Causes Occipital Cortical Malformation

Abstract

Occipital cortical malformation (OCCM) is a disease caused by malformations of cortical development characterized by polymicrogyria and pachygyria of the occipital lobes and childhood-onset seizures. The recessive or complex heterozygous variants of the LAMC3 gene are identified as the cause of OCCM. In the present study, we identified novel complex heterozygous variants (c.470G > A and c.4030 + 1G > A) of the LAMC3 gene in a Chinese female with childhood-onset seizures. Cranial magnetic resonance imaging was normal. Functional experiments confirmed that both variant sites caused premature truncation of the laminin γ3 chain. Bioinformatics analysis predicted 10 genes interacted with LAMC3 with an interaction score of 0.4 (P value = 1.0e–16). The proteins encoded by these genes were mainly located in the basement membrane and extracellular matrix component. Furthermore, the biological processes and molecular functions from gene ontology analysis indicated that laminin γ3 chain and related proteins played an important role in structural support and cellular processes through protein-containing complex binding and signaling receptor binding. KEGG pathway enrichment predicted that the LAMC3 gene variant was most likely to participate in the occurrence and development of OCCM through extracellular matrix receptor interaction and PI3K-Akt signaling pathway.

Prediction of high-risk liver cancer patients from their mutation profile: Benchmarking of mutation calling techniques

“…Moreover, the down-regulation of LAMC3 is correlated with the poor prognosis and metastasis in the ovarian cancer patients (Lei et al, 2021). A study also reveals that mutations associated with LAMC3 genes may cause PNH (a rare disorder of clonal stem cell in foetus), which may leads high mortality rate infection and premature birth (De Angelis et al, 2021;Qian et al, 2021). We also observed that mutations associated with LAMC3 significantly reduces the survival of patients with HR = 9.25 and p-value<0.001.…”

A New Case With Cortical Malformation Caused by Biallelic Variants in LAMC3

“…Until now, 7 unrelated families worldwide have been reported to exhibit cortical malformations due to LAMC3 variants. All these patients with LAMC3 variants exhibited cortical malformations involving the occipital lobe, except for the patient reported by Qian et al, 4 while Kasper et al 3 reported a patient with cortical malformation predominantly in the frontal lobe. In addition, a patient reported by Zamboni et al also exhibited cortical malformation in the frontal, parietal, and temporal lobes.…”

“…Clinical symptoms may arise later during infancy or even adulthood in milder cases. [1][2][3][4][5] Seizures, developmental delay, impaired visual function, and cognitive delays can also be observed in affected individuals. Variants in actin-associated or microtubule-associated genes have been associated with cortical malformation.…”

Prediction of risk-associated genes and high-risk liver cancer patients from their mutation profile: benchmarking of mutation calling techniques

“…Moreover, the down-regulation of LAMC3 is correlated with the poor prognosis and metastasis in the ovarian cancer patients [ 56 ]. A study also reveals that mutations associated with LAMC3 genes may cause paroxysmal nocturnal haemoglobinuria, a rare disorder of clonal stem cell in foetus, which may lead to high mortality rate infection and premature birth [ 57 , 58 ]. We also observed that mutations associated with LAMC3 significantly reduce the survival of patients with HR = 9.25 and P -value of 1.78E-06.…”