An 18 bps in-frame deletion mutation in RUNX2 gene is a population polymorphism rather than a pathogenic variant

Hashmi, Jamil Amjad; Almatrafi, Ahmad; Latif, Muhammad; Nasır, Abdul; Basit, Sulman

doi:10.1016/j.ejmg.2018.06.013

Cited by 10 publications

(3 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MutationTaster (Schwarz et al, 2014), Polyphen2 (Adzhubei et al, 2010) and SIFT (Ng, 2003) were used for further shortlisting of potentially deleterious variants. The procedure used for variant filtration is described in detail elsewhere (Alkhiary et al, 2017;Hashmi et al, 2019).…”

Section: Exome Sequencing and Data Analysismentioning

confidence: 99%

An intrafamilial phenotypic variability in Ellis‐Van Creveld syndrome due to a novel 27 bps deletion mutation

Zaka

Shahzad

Rao

et al. 2021

American J of Med Genetics Pt A

Self Cite

View full text Add to dashboard Cite

Ellis-van Creveld (EvC) syndrome is an autosomal recessive disease, characterized by ectodermal, skeletal, and cardiac anomalies. We report intrafamilial phenotypic variability in three new EvC syndrome cases. Affected males in this study showed only ectodermal abnormalities, whereas an affected female showed the classical presentation of EvC Syndrome, including bilateral postaxial polydactyly of hands and feet, and congenital heart defects. Whole exome sequencing was performed to identify the causative variant, followed by validation and segregation analysis using Sanger sequencing. A homozygous deletion variant (c.731_757del) was identified in exon 6 of the EVC gene (NM_153717.2). The identified variant is considered to be the most likely candidate variant for the EvC syndrome in the family based on previous reports validating the role of EVC variants in the EvC syndrome. The disease correctly segregated in the family members, as all affected members were homozygous, and obligate carriers were heterozygous. Our family is remarkable in highlighting the variable expressivity of the EvC phenotype within the same family, due to a homozygous deletion mutation in the EVC gene. The variable expressivity might be due to the

show abstract

Section: Exome Sequencing and Data Analysismentioning

confidence: 99%

An intrafamilial phenotypic variability in Ellis‐Van Creveld syndrome due to a novel 27 bps deletion mutation

Zaka

Shahzad

Rao

et al. 2021

American J of Med Genetics Pt A

Self Cite

View full text Add to dashboard Cite

show abstract

“…Approximately 200 ng genomic DNA of two affected and two unaffected members were taken for genotyping as per protocol described elsewhere. 26,27 Illumina genome studio and homozygosity mapper 28,29 were employed to detect common regions sharing homozygosity amongst the affected members.…”

Section: Whole Genome Single Nucleotide Polymorphism (Snp) Genotypingmentioning

confidence: 99%

Further Evidence of a Recessive Variant in COL1A1 as an Underlying Cause of Ehlers–Danlos Syndrome: A Report of a Saudi Founder Mutation

Almatrafi

Hashmi

Fadhli

et al. 2020

Global Medical Genetics

Self Cite

View full text Add to dashboard Cite

Ehlers–Danlos syndrome (EDS) is a group of clinically and genetically heterogeneous disorder of soft connective tissues. The hallmark clinical features of the EDS are hyperextensible skin, hypermobile joints, and fragile vessels. It exhibits associated symptoms including contractures of muscles, kyphoscoliosis, spondylodysplasia, dermatosparaxis, periodontitis, and arthrochalasia. The aim of this study is to determine the exact subtype of EDS by molecular genetic testing in a family segregating EDS in an autosomal recessive manner. Herein, we describe a family with two individuals afflicted with EDS. Whole exome sequencing identified a homozygous missense mutation (c.2050G > A; p.Glu684Lys) in the COL1A1 gene in both affected individuals, although heterozygous variants in the COL1A1 are known to cause EDS. Recently, only one report showed homozygous variant as an underlying cause of the EDS in two Saudi families. This is the second report of a homozygous variant in the COL1A1 gene in a family of Saudi origin. Heterozygous carriers of COL1A1 variant are asymptomatic. Interestingly, the homozygous variant identified previously and the one identified in this study are same (c.2050G > A). The identification of a unique homozygous mutation (c.2050G > A) in three Saudi families argues in favor of a founder effect.

show abstract

“…Variants obtained after exome sequencing of two affected individuals were filtered for pathogenic mutations. Standard procedure was used for variants filtration(Hashmi, Almatrafi, Latif, Nasir, & Basit, 2019).Variants which were found to have a frequency greater than 0.01 in databases of human genetic variation were filtered out. Moreover, variants with DP values greater than 20 were also excluded.…”

mentioning

confidence: 99%

A novel homozygous frameshift mutation in the DCC gene in a Pakistani family with autosomal recessive horizontal gaze palsy with progressive scoliosis‐2 with impaired intellectual development

Zaka

Shahzad

Rao

et al. 2020

American J of Med Genetics Pt A

Self Cite

View full text Add to dashboard Cite

Horizontal Gaze Palsy with Progressive Scoliosis-2 with Impaired Intellectual Development (HGPPS2) is a rare congenital disorder characterized by absence of conjugate horizontal eye movements, and progressive scoliosis developing in childhood and adolescence. We report three new patients with HGPPS2 in a consanguineous Pakistani family, presenting varying degrees of progressive scoliosis, developmental delays, horizontal gaze palsy, agenesis of corpus callosum, and absence of cerebral commissures. Analysis of genotyping data identified shared loss of heterozygosity (LOH) region on chromosomes 5p15.33-15.31, 6q11.2-12, and 18q21.1-21.3. A hypothesis-free, unbiased exome data analysis detected an insertion of nucleotide A (c.2399dupA) in exon 16 of the DCC gene. The insertion is predicted to cause frameshift p.(Asn800Lysfs*11). Interestingly, DCC gene is present in the LOH region on chromosome 18. Variant (c.2399dupA) in the DCC gene is considered as the most probable candidate variant for HGPPS2 based on the presence of DCC in the LOH region, previously reported role of DCC in HGPPS2, perfect segregation of candidate variant with the disease, prediction of variant pathogenicity, and absence of variant in variation databases. Sanger Sequencing confirmed the presence of the novel homozygous mutation in all three patients; the parents were heterozygous carriers of the mutation, in accordance with an autosomal recessive inheritance pattern. DCC encodes a netrin-1 receptor protein; its role in the development of the CNS has recently been established. Biallelic DCC mutations have previously been shown to cause HGPPS2. A novel homozygous variant in patients of the reported family extend the genotypic and phenotypic spectrum of HGPPS2.

show abstract

An 18 bps in-frame deletion mutation in RUNX2 gene is a population polymorphism rather than a pathogenic variant

Cited by 10 publications

References 25 publications

An intrafamilial phenotypic variability in Ellis‐Van Creveld syndrome due to a novel 27 bps deletion mutation

An intrafamilial phenotypic variability in Ellis‐Van Creveld syndrome due to a novel 27 bps deletion mutation

Further Evidence of a Recessive Variant in COL1A1 as an Underlying Cause of Ehlers–Danlos Syndrome: A Report of a Saudi Founder Mutation

A novel homozygous frameshift mutation in the DCC gene in a Pakistani family with autosomal recessive horizontal gaze palsy with progressive scoliosis‐2 with impaired intellectual development

Contact Info

Product

Resources

About