Primary and Secondary Microcephaly, Global Developmental Delay, and Seizure in Two Siblings Caused by a Novel Missense Variant in the ZNF335 Gene

Tavasoli, Ali Reza; Memar, Elmira Haji Esmaeil; Ashrafi, Mahmoud Reza; Hosseini, Soodeh; Haghighi, Ramin; Ghabeli, Homa; Pourbakhtyaran, Elham; Rasoulinezhad, Maryam; Mohammadi, Pouria; Heidari, Morteza

doi:10.1007/s12031-021-01955-y

Cited by 10 publications

(8 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An in‐house bioinformatics pipeline was used for bioinformatic analysis. Prioritization and filtering of the relevant variants were performed manually based on similar studies 18–20 . Variants were excluded by manual filtering on the annotated VCF file, considering the inheritance mode, clinical information, and phenotypes according to HPO terms (https://hpo.jax.org/app/), consequence and allele frequency of variants according to 1000Genome project, GnomAD, and ExAC databases.…”

Section: Methodsmentioning

confidence: 99%

“…Prioritization and filtering of the relevant variants were performed manually based on similar studies. 18 , 19 , 20 Variants were excluded by manual filtering on the annotated VCF file, considering the inheritance mode, clinical information, and phenotypes according to HPO terms ( https://hpo.jax.org/app/ ), consequence and allele frequency of variants according to 1000Genome project, GnomAD, and ExAC databases. After that, we classified the remaining variants according to the American College of Medical Genetics and Genomics (ACMG) guideline rules.…”

Section: Methodsmentioning

confidence: 99%

“…Prioritization and filtering of the relevant variants were performed manually based on similar studies. [18][19][20] Variants were excluded by manual filtering on the annotated VCF file, considering the inheritance mode, clinical information, and phenotypes according to HPO terms (https:// hpo. jax.…”

Section: Whole-exome Sequencing and Bioinformatics Analysismentioning

confidence: 99%

See 2 more Smart Citations

Expression assay of the COLQ in a family with congenital myasthenic syndrome and symptomatic carriers

Mohammadi,

Fateh,

Aghajani

et al. 2023

Clinical Case Reports

Self Cite

View full text Add to dashboard Cite

Key Clinical MessageCongenital myasthenic syndromes‐5 (CMS5) is a rare autosomal recessive heterogeneous disorder, caused by pathogenic variants in the COLQ that lead to skeletal muscle weakness and abnormal fatigability. The onset is usually from birth to childhood. Disease‐causing variants in the collagen‐like tail subunit are the most explained etiology in synaptic CMS, causing defected acetylcholinesterase. In this study whole‐exome sequencing (WES) was performed in an affected boy with muscle weakness, ophthalmoplegia, and bilateral ptosis and gene expression assay by qRT‐PCR was performed in entire family. A homozygous nonsense variant in the COLQ [NM_005677.4:c.679C>T], (p.Arg227Ter) was identified in the proband. Segregation analysis by Sanger sequencing confirmed the homozygous state in the proband and heterozygous state in his parents and four of the siblings. The mRNA expression level in the proband was 0.02 of a healthy person, and in the carriers were 0.42 of a healthy person. This study presents an Iranian family with two affected children and eight symptomatic carriers with attenuated mRNA expression. This study provides evidence that carriers of the COLQ disease‐causing variants could become symptomatic with some yet unknown pathogenesis mechanism and underscore the importance of further investigations to elucidate this mechanism.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Expression assay of the COLQ in a family with congenital myasthenic syndrome and symptomatic carriers

Mohammadi,

Fateh,

Aghajani

et al. 2023

Clinical Case Reports

Self Cite

View full text Add to dashboard Cite

show abstract

“…Then, Whole Exome Sequencing was performed by the Agilent SureSelect Human All Exon V7 Kit from Illumina and using the NovaSeq 6000 platform with an average depth of about 100x. Based on similar studies (Mohammadi et al 2021a, b, c;Tavasoli et al 2022), an in-house bioinformatics pipeline was performed by the following bioinformatics tools:…”

Section: Whole Exome Sequencing and Bioinformatics Analysismentioning

confidence: 99%

Epilepsia Partialis Continua a Clinical Feature of a Missense Variant in the ADCK3 Gene and Poor Response to Therapy

et al. 2022

Self Cite

View full text Add to dashboard Cite

Introduction Coenzyme Q10 deficiency can be due to mutations in Coenzyme Q10-biosynthesis genes (primary) or genes unrelated to biosynthesis (secondary). Primary Coenzyme Q10 deficiency-4 (COQ10D4), also known as autosomal recessive spinocerebellar ataxia-9 (SCAR9), is an autosomal recessive disorder caused by mutations in the ADCK3 gene. This disorder is characterized by several clinical manifestations such as severe infantile multisystemic illness, encephalomyopathy, isolated myopathy, cerebellar ataxia, or nephrotic syndrome. Methods In this study, whole-exome sequencing was performed in order to identify disease-causing variants in an affected girl with developmental regression and Epilepsia Partialis Continua (EPC). Next, Sanger sequencing method was used to confirm the identified variant in the patient and segregation analysis in her parents. Case PresentationThe proband is an affected 11-year-old girl with persistent seizures, EPC, and developmental regression including motor, cognition, and speech. Seizures were not controlled with various anticonvulsant drugs despite adequate dosing. Progressive cerebellar atrophy, stroke-like cortical involvement, multifocal hyperintense bright objects, and restriction in diffusion-weighted imaging (DWI) were seen in the brain magnetic resonance imaging (MRI). Conclusions A novel homozygous missense variant [NM_020247.5: c.814G>T; (p.Gly272Cys)] was identified within the ADCK3 gene, which is the first mutation in this gene in the Iranian population. Bioinformatics analysis showed this variant is damaging. Based on our patient, clinicians should consider genetic testing earlier to instant diagnosis and satisfactory treatment based on exact etiology to prevent further neurologic sequelae.

show abstract

“…Whole-exome sequencing yielded 11.7 Gb of data with 99.5% coverage of the target region and 99.1% of the target covered over 10 ×. Data quality control steps, co-segregation, and bioinformatics analysis were performed following the published literature and our previous published studies (8)(9)(10)(11). After preliminary screening, variants were further filtered by cardiomyopathy-related genes list as described in our previous study (12).…”

Section: Genetic Analysismentioning

confidence: 99%

Case report: Whole-exome sequencing identifies a novel DES mutation (p. E434K) in a Chinese family with cardiomyopathy and sudden cardiac death

Liu

Yu²,

Sheng³

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

BackgroundDesmin is an intermediate filament protein that plays a critical role in the stabilization of the sarcomeres and cell contacts in the cardiac intercalated disk. Mutated DES gene can cause hereditary cardiomyopathy with heterogeneous phenotypes, while the underlying molecular mechanisms requires further investigation.MethodsWe described a Chinese family present with cardiomyopathy and sudden cardiac death (SCD). Whole-exome sequencing (WES) and bioinformatics strategies were employed to explore the genetic entity of this family.ResultsAn unknown heterozygote missense variant (c.1300G > A; p. E434K) of DES gene was identified. The mutation cosegregates in this family. The mutation was predicted as pathogenic and was absent in our 200 healthy controls.ConclusionWe identified a novel DES mutation (p. E434K) in a Chinese family with cardiomyopathy and SCD. Our study not only provided a new case for the study of the relationship between DES mutations and hereditary cardiomyopathy but also broadened the spectrum of DES mutations.

show abstract

Primary and Secondary Microcephaly, Global Developmental Delay, and Seizure in Two Siblings Caused by a Novel Missense Variant in the ZNF335 Gene

Cited by 10 publications

References 19 publications

Expression assay of the COLQ in a family with congenital myasthenic syndrome and symptomatic carriers

Expression assay of the COLQ in a family with congenital myasthenic syndrome and symptomatic carriers

Epilepsia Partialis Continua a Clinical Feature of a Missense Variant in the ADCK3 Gene and Poor Response to Therapy

Case report: Whole-exome sequencing identifies a novel DES mutation (p. E434K) in a Chinese family with cardiomyopathy and sudden cardiac death

Contact Info

Product

Resources

About