Novel phenotype and genotype spectrum of WDR62 in two patients with associated primary autosomal recessive microcephaly

Aryan, Hajar; Zokaei, Shaghayegh; Farhud, Dariush D.; Keykhaei, Mohammad; Ashrafi, Mahmoud Reza; Rasulinezhad, Maryam; Hosseini, Seyyed Mohammad Mahdi; Razmara, Ehsan; Tavasoli, Ali Reza

doi:10.1007/s11845-021-02890-y

Cited by 3 publications

(1 citation statement)

References 44 publications

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“…The WDR62 gene is the second most frequent mutated gene in autosomal recessive PMs. Since the identification of the first patients [ 3 , 10 , 11 ], 156 individuals from 74 families, along with 66 different biallelic variants spread over the gene, have been reported (see synthesis in [ 53 , 84 ] and more recently [ 66 , 85 ]). Unlike ASPM , the missense and nonsense/frameshift variants of WDR62 exhibited equal representation.…”

Section: Aspm Wdr62 and Dynei...mentioning

confidence: 99%

Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size

Farcy,

Hachour,

Bahi-Buisson

et al. 2023

Cells

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Primary microcephalies (PMs) are defects in brain growth that are detectable at or before birth and are responsible for neurodevelopmental disorders. Most are caused by biallelic or, more rarely, dominant mutations in one of the likely hundreds of genes encoding PM proteins, i.e., ubiquitous centrosome or microtubule-associated proteins required for the division of neural progenitor cells in the embryonic brain. Here, we provide an overview of the different types of PMs, i.e., isolated PMs with or without malformations of cortical development and PMs associated with short stature (microcephalic dwarfism) or sensorineural disorders. We present an overview of the genetic, developmental, neurological, and cognitive aspects characterizing the most representative PMs. The analysis of phenotypic similarities and differences among patients has led scientists to elucidate the roles of these PM proteins in humans. Phenotypic similarities indicate possible redundant functions of a few of these proteins, such as ASPM and WDR62, which play roles only in determining brain size and structure. However, the protein pericentrin (PCNT) is equally required for determining brain and body size. Other PM proteins perform both functions, albeit to different degrees. Finally, by comparing phenotypes, we considered the interrelationships among these proteins.

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Section: Aspm Wdr62 and Dynei...mentioning

confidence: 99%

Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size

Farcy,

Hachour,

Bahi-Buisson

et al. 2023

Cells

View full text Add to dashboard Cite

show abstract

Molecular genetics, neuroimaging outcomes, and structural analyses of novel and recurrent variants of WDR62 gene in two consanguineous Pakistani families with autosomal recessive primary microcephaly

Aslam,

Saeed,

Saeed

et al. 2024

Mol Biol Rep

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Congenital Microcephaly: A Debate on Diagnostic Challenges and Etiological Paradigm of the Shift from Isolated/Non-Syndromic to Syndromic Microcephaly

Asif

Abdullah

Nürnberg

et al. 2023

Cells

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Congenital microcephaly (CM) exhibits broad clinical and genetic heterogeneity and is thus categorized into several subtypes. However, the recent bloom of disease–gene discoveries has revealed more overlaps than differences in the underlying genetic architecture for these clinical sub-categories, complicating the differential diagnosis. Moreover, the mechanism of the paradigm shift from a brain-restricted to a multi-organ phenotype is only vaguely understood. This review article highlights the critical factors considered while defining CM subtypes. It also presents possible arguments on long-standing questions of the brain-specific nature of CM caused by a dysfunction of the ubiquitously expressed proteins. We argue that brain-specific splicing events and organ-restricted protein expression may contribute in part to disparate clinical manifestations. We also highlight the role of genetic modifiers and de novo variants in the multi-organ phenotype of CM and emphasize their consideration in molecular characterization. This review thus attempts to expand our understanding of the phenotypic and etiological variability in CM and invites the development of more comprehensive guidelines.

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Novel phenotype and genotype spectrum of WDR62 in two patients with associated primary autosomal recessive microcephaly

Cited by 3 publications

References 44 publications

Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size

Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size

Molecular genetics, neuroimaging outcomes, and structural analyses of novel and recurrent variants of WDR62 gene in two consanguineous Pakistani families with autosomal recessive primary microcephaly

Congenital Microcephaly: A Debate on Diagnostic Challenges and Etiological Paradigm of the Shift from Isolated/Non-Syndromic to Syndromic Microcephaly

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