Myelomeningocele among Pakistani population

Abstract

Objective: To investigate the mutation in Vangl1 gene in patients of myelomeningocele. Method: The cross-sectional study was conducted from July 2017 to December 2017 in the Dow Diagnostic and Research Laboratory, Karachi, after approval from the ethics review committee of Dow University of Health Sciences, Karachi, and comprised clinically diagnosed infants and 10 healthy individuals from the outpatient department of Jinnah Postgraduate Medical Centre, Karachi. Several anatomical parameters were considered, such as size and site of the cyst. Blood samples were drawn and polymerase chain reaction was conducted for the identification of mutation in Vangl1 gene. Mutation analysis was carried out by aligning the sequence with the reference sequence. Results: Of the 60 subjects, 50(83.3%) were cases with age range 0-10 years, and 10(16.6%) were age matched controls. Majority of the patients 44 (88%) were aged <1 year. Novel mutation in Vangl1 gene was identified at position 239, showing the substitution of valine with glycineV239G. Lumbar region was the most common site for the presentation of myelomeningocele in most of the patients 46(92%). Conclusion: The rare mutation of myelomeningocele was found present in the sample, and the disease was found mostly in the lumbar region. Key Words: Myelomeningocele, Neural tube disorders, Valine, Glycine, Mutation.

Identification and functional analysis of rare HECTD1 missense variants in human neural tube defects

“…Many NTD candidate genes are relatively tolerant of missense variation. For instance, multiple VANGL1 missense variants have been identified in NTD cases, and the pathogenesis of many of these variants has been validated in numerous studies (Bartsch et al 2012 ; Cai et al 2014 ; Cheng et al 2021 ; De Marco et al 2014 ; Doudney et al 2005 ; Fatima et al 2022 ; Humphries et al 2020 ; Iliescu et al 2014 , 2011 ; Kibar et al 2007 , 2009 ; Merello et al 2015 ; Reynolds et al 2010 ; Tian et al 2020a , b ; Wang et al 2018 ). VANGL1 tolerates missense but not loss of function (LOF) variants with a missense Z score of 0.59 but a loss intolerance probability (pLI) scores close to 1 (0.91) and a LOF observed/expected upper bound fraction (LOEUF) score of 0.53.…”

Identification and Functional Analysis of Rare HECTD1 Missense Variants in Human Neural Tube Defects

“…However, an analysis of the Genome Aggregation Database (gnomAD v4.0.0) ( Chen et al 2022 ; Karczewski et al 2020 ) reveals that many NTD candidate genes tolerate missense variation (Supplemental Table 1). For instance, multiple VANGL1 missense variants have been identified in NTD cases and the pathogenesis of many of these variants was validated in experimental assays ( Bartsch et al 2012 ; Cai et al 2014 ; Cheng et al 2021 ; De Marco et al 2014 ; Doudney et al 2005 ; Fatima et al 2022 ; Humphries et al 2020 ; Iliescu et al 2014 ; Iliescu et al 2011 ; Kibar et al 2009 ; Kibar et al 2007 ; Merello et al 2015 ; Reynolds et al 2010 ; Tian et al 2020a ; Tian et al 2020b ; Wang et al 2018 ). VANGL1 tolerates missense but not loss of function (LOF) variants with a missense Z score of 0.59 but a loss intolerance probability (pLI) score close to 1 (0.91) and a LOF observed/expected upper bound fraction (LOEUF) score of 0.53.…”