A possible founder mutation in FZD6 gene in a Turkish family with autosomal recessive nail dysplasia

Abstract

BackgroundAutosomal recessive nail dysplasia is characterized by thick and hard nails with a very slow growth on the hands and feet. Mutations in FZD6 gene were found to be associated with autosomal recessive nail dysplasia in 2011. Presently, only seven mutations have been reported in FZD6 gene; five mutations are clustered in the C-terminus, one is at the seventh transmembrane domain, and another is at the very beginning of third extracellular loop.MethodsWhole exome sequencing (WES) was applied to the index case, her one affected sister and her healthy consanguineous parents. The mutation was verified via Sanger sequencing. Molecular dynamics simulations of the predicted structures of native and mutant proteins were compared to gain insight into the pathogenicity mechanism of the mutation.ResultsHere, we report a homozygous 8 bp deletion mutation, p.Gly559Aspfs*16; c.1676_1683delGAACCAGC, in FZD6 gene which causes a frameshift and creates a premature stop codon at position 16 of the new reading frame. Our molecular dynamics calculations predict that the pathogenicity of this frameshift mutation may be caused by the change in entropy of the protein with negative manner, disturbing the C-terminal domain structure, and hence interaction partners of FZD6.ConclusionWe identified a homozygous deletion mutation in FZD6 in a consanguineous Turkish family with nail dysplasia. We also provide a molecular mechanism about the effects of the deletion on the protein structure and its possible motions. This study provides a pathogenicity mechanism for this mutation in nail dysplasia for the first time.Electronic supplementary materialThe online version of this article (10.1186/s12881-019-0746-6) contains supplementary material, which is available to authorized users.

Long non‐coding RNA linc00659 promotes tumour progression by regulating FZD6/Wnt/β‐catenin signalling pathway in colorectal cancer via m6A reader IGF2BP1

“…As a minority member of the family, FZD6 is a negative regulator of the typical Wnt/β-catenin signalling cascade. 29,30 It has been reported that FZD6 is upregulated in some cancer types, such as colorectal cancer, pancreatic cancer or esophageal cancer, and promotes the growth and metastasis of cancer cells, and it is also associated with low overall survival. 30 In a study by Cheng et al, 31 FZD6 as an inhibitor of the Wnt signalling pathway was extensively linked to miRNAs, and inhibition of FZD6 can reduce the tumourigenic behavior of GB in vitro and in vivo.…”

“…We studied one of these candidates, FZD6, which is a member of the “frizzled” gene family; this family encodes proteins with seven transmembrane domains and an N‐terminal extracellular domain encoded by a cysteine‐rich domain. As a minority member of the family, FZD6 is a negative regulator of the typical Wnt/β‐catenin signalling cascade 29,30 . It has been reported that FZD6 is upregulated in some cancer types, such as colorectal cancer, pancreatic cancer or esophageal cancer, and promotes the growth and metastasis of cancer cells, and it is also associated with low overall survival 30 .…”

Genome-Wide Search for Associations with Meat Production Parameters in Karachaevsky Sheep Breed Using the Illumina BeadChip 600 K

“…Directly, receptor 6 is a negative regulator of the Wnt/β-catenin signaling cascade, thereby inhibiting cell proliferation and apoptosis. Deletion in this gene was found to be associated with the development of autosomal recessive nail dysplasia [ 31 ]. FZD6 has also been implicated in the development of malignant esophageal carcinoma in humans [ 32 ].…”