scholarly journals Human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
K. S. Au ◽  
L. Hebert ◽  
P. Hillman ◽  
C. Baker ◽  
M. R. Brown ◽  
...  
Keyword(s):  
Cell Migration ◽  
Wnt Signaling ◽  
Candidate Genes ◽  
Biological Function ◽  
Disease Risk ◽  
Neural Tube Closure ◽  
Study Cohort ◽  
Gene Transcription Regulation ◽  
Genetic And Environmental Factors ◽  
Tube Closure

AbstractMyelomeningocele (MMC) affects one in 1000 newborns annually worldwide and each surviving child faces tremendous lifetime medical and caregiving burdens. Both genetic and environmental factors contribute to disease risk but the mechanism is unclear. This study examined 506 MMC subjects for ultra-rare deleterious variants (URDVs, absent in gnomAD v2.1.1 controls that have Combined Annotation Dependent Depletion score ≥ 20) in candidate genes either known to cause abnormal neural tube closure in animals or previously associated with human MMC in the current study cohort. Approximately 70% of the study subjects carried one to nine URDVs among 302 candidate genes. Half of the study subjects carried heterozygous URDVs in multiple genes involved in the structure and/or function of cilium, cytoskeleton, extracellular matrix, WNT signaling, and/or cell migration. Another 20% of the study subjects carried heterozygous URDVs in candidate genes associated with gene transcription regulation, folate metabolism, or glucose metabolism. Presence of URDVs in the candidate genes involving these biological function groups may elevate the risk of developing myelomeningocele in the study cohort.

scholarly journals Fate Specification of Neural Plate Border by Canonical Wnt Signaling and Grhl3 is Crucial for Neural Tube Closure

EBioMedicine ◽  
2015 ◽  
Vol 2 (6) ◽  
pp. 513-527 ◽  
Author(s):  
Chiharu Kimura-Yoshida ◽  
Kyoko Mochida ◽  
Kristina Ellwanger ◽  
Christof Niehrs ◽  
Isao Matsuo
Keyword(s):  
Wnt Signaling ◽  
Neural Tube ◽  
Neural Plate ◽  
Neural Tube Closure ◽  
Canonical Wnt Signaling ◽  
Fate Specification ◽  
Neural Plate Border ◽  
Canonical Wnt ◽  
Tube Closure

scholarly journals LRP6 exerts non-canonical effects on Wnt signaling during neural tube closure

2013 ◽  
Vol 22 (21) ◽  
pp. 4267-4281 ◽  
Author(s):  
Jason D. Gray ◽  
Stanislav Kholmanskikh ◽  
Bozena S. Castaldo ◽  
Alex Hansler ◽  
Heekyung Chung ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Neural Tube ◽  
Neural Tube Closure ◽  
Tube Closure

SKIN MELANOMA INCIDENCE IN WORKERS OCUPATIONALLY EXPOSED TO IONIZING RADIATION OVER A PROLONGED PERIOD

2019 ◽  
Vol 65 (3) ◽  
pp. 441-446
Author(s):  
Valentina Rybkina ◽  
Tamara Azizova ◽  
Yevgeniya Grigoreva
Keyword(s):  
Ionizing Radiation ◽  
Gamma Rays ◽  
Disease Risk ◽  
Incidence Rates ◽  
Study Cohort ◽  
Calendar Period ◽  
Skin Melanoma ◽  
Melanoma Incidence ◽  
Occupationally Exposed

Purpose of the study. The study is aimed to investigate skin melanoma incidence in workers occupationally exposed to radiation over a prolonged period. Materials and methods. Skin melanoma incidence was studied in a cohort of workers first employed at nuclear facility Mayak Production Association (PA) between 1948 and 1982 who had been followed up till 31.12.2013 (22,377 individuals). Mean cumulative doses from external gamma-rays over the whole follow-up period were 0.54±0.001 Sv in males and 0.44±0.002 Sv in females. Incident rates for skin melanoma were analyzed by sex, attained age, calendar period of diagnostics and radiation dose using worldwide standard and the direct standardization technique. Results. 60 skin melanoma cases (37 in males and 23 in females) were registered in the study cohort over the whole follow-up period. The standardized skin melanoma incident rate was 8.51±1.46 in males and 8.78±2.27 in females per 100000 workers revealing statistically higher rates compared to corresponding rates for general populations of the Russian Federation, Urals Federal District and Chelyabinsk region. Skin melanoma incidence was significantly increased in the period of 1994 - 2013 as compared to the period of 1974 - 1993. Skin melanoma incidence excess in females was greater than that for males. Skin melanoma incidence increment in females was mostly driven by modifications of disease occurrence risk while in males it was driven by a combined effect of age pattern modifications in the study cohort and increase of disease risk. Conclusions. Skin melanoma incidence rates in the cohort of workers occupationally exposed to ionizing radiation over a prolonged period were associated with sex and attained age workers and the calendar period of diagnostics. No significant association of skin melanoma incidence with dose from external gamma-rays was observed. A significantly increasing trend was observed for skin melanoma incidence by the end of the follow-up in both males and females.

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