<i>Biallelic ZNF335</i> mutations cause basal ganglia abnormality with progressive cerebral/cerebellar atrophy

Çağlayan, Ahmet Okay; Yaghouti, Kourosh; Koçkaya, Tanyel; Kemer, Demet; Çankaya, Tufan; Ameziane, Najim; Çoğulu, Özgür; Çöker, Mahmut; Yalçınkaya, Cengiz

doi:10.1080/01677063.2020.1833006

Cited by 4 publications

(5 citation statements)

References 32 publications

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“…Cerebral atrophy with a simplified gyral pattern, as observed in our patient, was also reported by multiple other cases (Caglayan et al, 2021; Rana et al, 2019; Sato et al, 2016; Stouffs et al, 2018; Yang et al, 2012) reinforcing the role of ZNF335 in neurogenesis. Cerebellar atrophy has been consistently reported but was not observed in our patient.…”

Section: Discussionsupporting

confidence: 89%

“…More so, Tavasoli et al (2022) demonstrated isolated cerebellar atrophy in both children with primary and secondary microcephaly. Caglayan et al (2021) highlighted the progressive cerebral and cerebellar atrophy, which further underscores the role of ZNF335 in neurodegeneration, as noted by Yang et al (2012). Commoner causes of microcephaly such as congenital infections usually present with intracerebral calcifications and white matter T2 hyperintensities.…”

Section: Discussionmentioning

confidence: 82%

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Novel biallelic ZNF335 variant causing primary microcephaly: A case report and radiological review

Patel,

Gripp,

Wadman

et al. 2024

American J of Med Genetics Pt A

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Biallelic pathogenic variants in ZNF335 are one of the genetic causes of microcephaly, reported only in the past decade. It regulates neural progenitor proliferation and neurogenesis by interacting with a H3K4 methyltransferase complex. Biallelic pathogenic ZNF335 variants predispose to neuronal cell death and aberrant differentiation, thus causing secondary microcephaly. These neurodevelopmental anomalies lead to imaging findings in the cortex, posterior fossa, and basal ganglia. We report an individual of Nepalese ancestry with a novel homozygous ZNF335 variant (c.3591 + 2dup) (p.?) (NM_022095.3) which on further RNA analysis confirmed a splice site variant in intron 23. The patient presented with primary microcephaly with atrophic cerebral hemispheres, oversimplification of gyri, basal ganglia, and corpus callosal atrophy. Literature review on the topic revealed a spectrum of brain abnormalities, which can present either with a primary or secondary microcephaly depending upon the underlying genetic variant.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 82%

Novel biallelic ZNF335 variant causing primary microcephaly: A case report and radiological review

Patel,

Gripp,

Wadman

et al. 2024

American J of Med Genetics Pt A

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“…However, the increased number of reported mutations and the ongoing neuroimaging of MCPH individuals reveal further brain malformations ( Table 2 ). Some of these structural changes point toward the causative MCPH gene (e.g., the association between malformations of basal ganglia and mutations in gene encoding zinc finger-335 protein ( ZNF335 ; MCPH10 ) ( Sato et al, 2016 ; Stouffs et al, 2018 ; Rana et al, 2019 ; Caglayan et al, 2021 )). The increasing number of reported brain malformations in MCPH individuals widens its pathogenesis spectrum.…”

Section: Brain Phenotype In Individuals With Microcephaly Primary Hereditarymentioning

confidence: 99%

Autosomal Recessive Primary Microcephaly: Not Just a Small Brain

Zaqout

Kaindl

2022

Front. Cell Dev. Biol.

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Microcephaly or reduced head circumference results from a multitude of abnormal developmental processes affecting brain growth and/or leading to brain atrophy. Autosomal recessive primary microcephaly (MCPH) is the prototype of isolated primary (congenital) microcephaly, affecting predominantly the cerebral cortex. For MCPH, an accelerating number of mutated genes emerge annually, and they are involved in crucial steps of neurogenesis. In this review article, we provide a deeper look into the microcephalic MCPH brain. We explore cytoarchitecture focusing on the cerebral cortex and discuss diverse processes occurring at the level of neural progenitors, early generated and mature neurons, and glial cells. We aim to thereby give an overview of current knowledge in MCPH phenotype and normal brain growth.

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“…The second VUS was inherited from the mother and is also present in the general control population (ExAC, 0.08%). Even as four out of five prediction tools indicate that this latter VUS could be pathogenic (►Table 1), compound heterozygous (or homozygous) mutations in this gene have been linked to basal ganglia abnormalities, 12 agyria with prominent extraaxial spaces, and cerebral/cerebellar hypoplasia or hypomyelination, 13 which do not overlap with our patient's phenotype.…”

Section: Genementioning

confidence: 88%

“…However, computational analyses revealed that one of the two VUS are likely benign and the patient's phenotype did not overlap with those of reported PWE and ZNF335 mutations, showing clear brain anomalies such as microcephaly and/or invisible basal ganglia. 12,13 Subsequently, WES revealed three VUS in three genes (IGLON5, SLC7A3, and CACNA1H). Our in silico predictions showed that the IGLON5 and CACNA1H variants are likely benign and also present in a healthy control population, in clear contrast to the SLC7A3 variant (►Table 1).…”

Section: Discussionmentioning

confidence: 99%

SLC7A3: In Silico Prediction of a Potential New Cause of Childhood Epilepsy

et al. 2021

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We report an in-depth genetic analysis in an 11-year-old boy with drug-resistant, generalized seizures and developmental disability. Three distinct variants of unknown clinical significance (VUS) were detected by whole exome sequencing (WES) but not by initial genetic analyses (microarray and epilepsy gene panel). These variants involve the SLC7A3, CACNA1H, and IGLON5 genes, which were subsequently evaluated by computational analyses using the InterVar tool and MutationTaster. While future functional studies are necessary to prove the pathogenicity of a certain VUS, segregation analyses over three generations and in silico predictions suggest the X-linked gene SLC7A3 (transmembrane solute carrier transporter) as the likely culprit gene in this patient. In addition, a search via GeneMatcher unveiled two additional patients with a VUS in SLC7A3. We propose SLC7A3 as a likely candidate gene for epilepsy and/or developmental/cognitive delay and provide an overview of the 27 SLC genes related to epilepsy by other preclinical and/or clinical studies.

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Biallelic ZNF335 mutations cause basal ganglia abnormality with progressive cerebral/cerebellar atrophy

Cited by 4 publications

References 32 publications

Novel biallelic ZNF335 variant causing primary microcephaly: A case report and radiological review

Novel biallelic ZNF335 variant causing primary microcephaly: A case report and radiological review

Autosomal Recessive Primary Microcephaly: Not Just a Small Brain

SLC7A3: In Silico Prediction of a Potential New Cause of Childhood Epilepsy

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