Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Primary and Secondary Microcephaly, Global Developmental Delay, and Seizure in Two Siblings Caused by a Novel Missense Variant in the Znf335 Gene Publisher Pubmed



Tavasoli AR1 ; Memar EHE1 ; Ashrafi MR1 ; Hosseini SMM1 ; Haghighi R1 ; Ghabeli H1 ; Pourbakhtyaran E1 ; Rasoulinezhad M1 ; Mohammadi P2 ; Heidari M1
Authors
Show Affiliations
Authors Affiliations
  1. 1. Pediatric Neurology Division, Children’s Medical Center, Pediatrics Center of Excellence, Myelin Disorders Clinic, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Jalah-Al Ahmad Hwy, Tehran, 14117-1316, Iran

Source: Journal of Molecular Neuroscience Published:2022


Abstract

Autosomal recessive microcephaly is a rare clinical condition, which is characterized by reduced brain size that can be associated with delayed intellectual ability, developmental delay, and seizure. In this study, we describe two siblings with microcephaly: a 12-year-old girl with primary microcephaly, and a 7-year-old boy with secondary microcephaly, whose episodes of seizure and neurodevelopmental regression started at 6 years and 6 months of age, respectively. The interesting finding in these siblings was two different presentations of the same variant: one case with primary and one case with secondary microcephaly. Whole-exome sequencing was performed in order to identify causative variants in one family having two affected siblings with microcephaly. Confirmation of the identified variant in the ZNF335 gene in the proband and her affected brother and segregation analysis in the family were performed using the Sanger sequencing method. In both patients, a novel homozygous missense variant, [NM_022095.4: c.3346G>A; p.(Gly1116Arg)], in the ZNF335 gene was identified. The p.(Gly1116Arg) variant causes a defect in the last zinc finger domain of the protein. Conservation analysis by ConSurf server and UCSC genome browser revealed that Gly1116 is a highly conserved amino acid among different species. Different in-silico prediction tools and bioinformatics analysis predicted this variant as damaging. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Related Docs
View other Related Docs
1. Clinical and Molecular Findings of Autosomal Recessive Spastic Ataxia of Charlevoix Saguenay: An Iranian Case Series Expanding the Genetic and Neuroimaging Spectra, Cerebellum (2023)
2. Expanding the Genetic Spectrum of Giant Axonal Neuropathy: Two Novel Variants in Iranian Families, Molecular Genetics and Genomic Medicine (2023)
3. A Mutational Hotspot in the Lamp2 Gene: Unravelling Intrafamilial Phenotypic Variation and Global Distribution of the C.877C>T Variant: A Descriptive Study, Cell Journal (2024)
4. Novel Phenotype and Genotype Spectrum of Wdr62 in Two Patients With Associated Primary Autosomal Recessive Microcephaly, Irish Journal of Medical Science (2022)
5. Crystallographic Modeling of the Pnpt1:C.1453A>G Variant As a Cause of Mitochondrial Dysfunction and Autosomal Recessive Deafness; Expanding the Neuroimaging and Clinical Features, Mitochondrion (2021)
6. Novel Stag3 Variant Associated With Primary Ovarian Insufficiency and Non-Obstructive Azoospermia in an Iranian Consanguineous Family, Gene (2022)
7. Extending and Outlining the Genotypic and Phenotypic Spectrum of Novel Mutations of Nalcn Gene in Ihprf1 Syndrome: Identifying Recurrent Urinary Tract Infection, Neurological Sciences (2023)
8. Expanding the Neuroimaging Findings of Guanidinoacetate Methyltransferase Deficiency in an Iranian Girl With a Homozygous Frameshift Variant in the Gamt, Neurogenetics (2023)
Experts (# of related papers)
View all Related Experts
Ali Reza Tavasoli (18)
Mahmoudreza Ashrafi (14)
Other Related Docs
9. Acer3-Related Leukoencephalopathy: Expanding the Clinical and Imaging Findings Spectrum Due to Novel Variants, Human Genomics (2021)
10. Next Generation Sequencing Elucidated a Clinically Undiagnosed Metabolic Disorder - an Iranian Family With Hereditary Orotic Aciduria, Gene Reports (2019)
11. Novel Lama2 Gene Mutations Associated With Merosin-Deficient Congenital Muscular Dystrophy, Iranian Biomedical Journal (2018)
12. Expanding the Clinical and Neuroimaging Features of Nkx6-2-Related Hereditary Spastic Ataxia Type 8, European Journal of Medical Genetics (2020)
13. Identification of a Novel Homozygous Gls Gene Variant Associated With Developmental and Epileptic Encephalopathy (Dee) Type 71, Neurogenetics (2024)
14. Epilepsia Partialis Continua a Clinical Feature of a Missense Variant in the Adck3 Gene and Poor Response to Therapy, Journal of Molecular Neuroscience (2022)
15. Genetic Analysis of Forty Mlpa-Negative Duchenne Muscular Dystrophy Patients by Whole-Exome Sequencing, Journal of Molecular Neuroscience (2022)
16. Spinal Muscular Atrophy With Progressive Myoclonic Epilepsy (Sma-Pme): Three New Cases and Review of the Mutational Spectrum, Italian Journal of Pediatrics (2023)
17. Whole Exome Sequencing Reveals a Xpnpep3 Novel Mutation Causing Nephronophthisis in a Pediatric Patient, Iranian Biomedical Journal (2020)
18. A Novel Compound Heterozygote Mutation in the Arsb Gene in a Patient With Maroteaux-Lamy Syndrome and Its Insilico Evaluation, Meta Gene (2018)
19. Expanding Phenotype Heterogeneity of Nars2 by Presenting Subdural Hematoma and Parenchymal Hemorrhage, Journal of Clinical Laboratory Analysis (2023)
20. Il10 Low-Frequency Variants in Behcet's Disease Patients, International Journal of Rheumatic Diseases (2017)
21. Gjb2 Mutations Causing Autosomal Recessive Non-Syndromic Hearing Loss (Arnshl) in Two Iranian Populations: Report of Two Novel Variants, International Journal of Pediatric Otorhinolaryngology (2018)
22. Whole Exome Sequencing for Mutation Screening in Hemophagocytic Lymphohistiocytosis, Iranian Journal of Pediatric Hematology and Oncology (2020)
23. Association of Tmprss2 Gene Polymorphisms With Covid-19 Severity and Mortality: A Case-Control Study With Computational Analyses, Applied Biochemistry and Biotechnology (2022)
24. A Novel Deletion Variant in Cln3 With Highly Variable Expressivity Is Responsible for Juvenile Neuronal Ceroid Lipofuscinoses, Acta Neurologica Belgica (2021)
25. Novel Imaging and Clinical Phenotypes of Condsias Disorder Caused by a Homozygous Frameshift Variant of Adprhl2: A Case Report, BMC Neurology (2020)
26. Novel Manifestations of Warburg Micro Syndrome Type 1 Caused by a New Splicing Variant of Rab3gap1: A Case Report, BMC Neurology (2021)
27. Autozygosity Mapping of Methylmalonic Acidemia Associated Genes by Short Tandem Repeat Markers Facilitates the Identification of Five Novel Mutations in an Iranian Patient Cohort, Metabolic Brain Disease (2018)
28. Identification of a Novel Missense C.386G > a Variant in a Boy With the Pomgnt1-Related Muscular Dystrophy-Dystroglycanopathy, Acta Neurologica Belgica (2021)
29. Structural Modeling of Human Akap3 Protein and in Silico Analysis of Single Nucleotide Polymorphisms Associated With Sperm Motility, Scientific Reports (2022)
30. Comprehensive Review and Expanding the Genetic Landscape of Cornelia-De-Lange Spectrum: Insights From Novel Mutations and Skin Biopsy in Exome-Negative Cases, BMC Medical Genomics (2024)
31. Genetic Testing of Leukodystrophies Unraveling Extensive Heterogeneity in a Large Cohort and Report of Five Common Diseases and 38 Novel Variants, Scientific Reports (2021)
32. Novel Mutation C.7348C>T in Nf1 Gene Identified by Whole-Exome Sequencing in Patient With Overlapping Clinical Symptoms of Neurofibromatosis Type 1 and Bannayan–Riley–Ruvalcaba Syndrome, Cytology and Genetics (2020)
33. Rpe65 and Retinal Dystrophy: Report of New and Recurrent Mutations, Journal of Gene Medicine (2020)
34. Genotypes of European and Iranian Patients With Type 3 Von Willebrand Disease Enrolled in 3Winters-Ips, Blood Advances (2021)
35. Molecular Genetic Study of Glutaric Aciduria, Type I: Identification of a Novel Mutation, Journal of Cellular Biochemistry (2019)
36. Persistent Basal Ganglia Involvement in Aminoacylase-1 Deficiency: Expanding Imaging Findings and Review of Literature, Irish Journal of Medical Science (2024)
37. Identification of Six Novel Mutations in Iranian Patients With Maple Syrup Urine Disease and Their in Silico Analysis, Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis (2016)
38. A Novel Variant in the Pah Gene Causing Phenylketonuria in an Iranian Pedigree, Avicenna Journal of Medical Biotechnology (2017)
39. Exome Sequencing Reveals Novel Rare Variants in Iranian Familial Multiple Sclerosis: The Importance of Pold2 in the Disease Pathogenesis, Genomics (2021)
40. A Novel Missense Variant in the Lmnb2 Gene Causes Progressive Myoclonus Epilepsy, Acta Neurologica Belgica (2022)
41. Nckap1l Defects Lead to a Novel Syndrome Combining Immunodeficiency, Lymphoproliferation, and Hyperinflammation, Journal of Experimental Medicine (2020)
42. Genetic Homozygosity in a Diverse Population: An Experience of Long Qt Syndrome, International Journal of Cardiology (2020)
43. A Comprehensive Study of Mutation and Phenotypic Heterogeneity of Childhood Mitochondrial Leukodystrophies, Brain and Development (2024)
44. A Bioinformatics Approach to Prioritize Single Nucleotide Polymorphisms in Tlrs Signaling Pathway Genes, International Journal of Molecular and Cellular Medicine (2016)
45. The First Iranian Patient With You-Hoover-Fong Syndrome and a Review of the Literature on 27 Cases: Expanding the Genotypic and Phenotypic Spectrum, Neurological Sciences (2024)