Novel &lt;b&gt;&lt;i&gt;KIF7&lt;/i&gt;&lt;/b&gt; Mutation in a Tunisian Boy with Acrocallosal Syndrome: Case Report and Review of the Literature

Ibisler, Aysegül; Hehr, Ute; Barth, Alfred; Koch, Margarete; Epplen, Jörg T.; Hoffjan, Sabine

doi:10.1159/000439414

Cited by 17 publications

(13 citation statements)

References 29 publications

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“…Its homozygous or compound heterozygous mutations, the former of which was recently identified in a six-month-old Tunisian boy with ACLS, lead to the spectrum of defects characteristic of this syndrome, such as macrocephaly, prominent forehead, depressed nasal bridge, and hypertelorism. ACLS belongs to the group of ciliopathies related to Joubert syndrome (JBTS; MIM 213300) [ 25 , 26 ]. Due to a broad range of phenotypes in patients with Kif7 mutations, it may be useful to identify a group of Kif7 -related ciliopathies.…”

Section: Resultsmentioning

confidence: 99%

Corpus Callosum Agenesis: An Insight into the Etiology and Spectrum of Symptoms

et al. 2020

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Brain hemispheres are connected by commissural structures, which consist of white matter fiber tracts that spread excitatory stimuli to various regions of the cortex. This allows an interaction between the two cerebral halves. The largest commissure is the corpus callosum (CC) which is located inferior to the longitudinal fissure, serving as its lower border. Sometimes this structure is not completely developed, which results in the condition known as agenesis of the corpus callosum (ACC). The aim of this paper was to review the latest discoveries related to the genetic and metabolic background of ACC, including the genotype/phenotype correlations as well as the clinical and imaging symptomatology. Due to various factors, including genetic defects and metabolic diseases, the development of CC may be impaired in many ways, which results in complete or partial ACC. This creates several clinical implications, depending on the specificity of the malformation and other defects in patients. Epilepsy, motor impairment and intellectual disability are the most prevalent. However, an asymptomatic course of the disease is even more common. ACC presents with characteristic images on ultrasound and magnetic resonance imaging (MRI).

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Section: Resultsmentioning

confidence: 99%

Corpus Callosum Agenesis: An Insight into the Etiology and Spectrum of Symptoms

et al. 2020

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“…To our knowledge, KIF7, a member of the kinesin-4 family and an evolutionarily conserved component of the core Hh signal transduction pathway, is, to date, the only molecule known to control both cilia length and Hh signaling (21). Mutations in KIF7 have been reported in different ciliopathies associated with perinatal lethality, including fetal hydrolethalus, Acrocallosal syndrome and JBS (19,20,(71)(72)(73)(74)(75)(76). Intriguingly, fibroblasts from Acrocallosal syndrome patients show upregulation of direct targets of Hh signaling and longer cilia (20).…”

Section: Discussionmentioning

confidence: 99%

The deubiquitinating enzyme Usp14 controls ciliogenesis and Hedgehog signaling

Massa

Tammaro

Prado

et al. 2018

Human Molecular Genetics

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Primary cilia are hair-like organelles that play crucial roles in vertebrate development, organogenesis and when dysfunctional result in pleiotropic human genetic disorders called ciliopathies, characterized by overlapping phenotypes, such as renal and hepatic cysts, skeletal defects, retinal degeneration and central nervous system malformations. Primary cilia act as communication hubs to transfer extracellular signals into intracellular responses and are essential for Hedgehog (Hh) signal transduction in mammals. Despite the renewed interest in this ancient organelle of growing biomedical importance, the molecular mechanisms that trigger cilia formation, extension and ciliary signal transduction are still not fully understood. Here we provide, for the first time, evidence that the deubiquitinase ubiquitin-specific protease-14 (Usp14), a major regulator of the ubiquitin proteasome system (UPS), controls ciliogenesis, cilia elongation and Hh signal transduction. Moreover, we show that pharmacological inhibition of Usp14 positively affects Hh signal transduction in a model of autosomal dominant polycystic kidney disease. These findings provide new insight into the spectrum of action of UPS in cilia biology and may provide novel opportunities for therapeutic intervention in human conditions associated with ciliary dysfunction.

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“…KIF1A-related disorders are relatively rare in the general population, but males with pathogenic KIF1A variations have been observed to have tiny testes or penises, as well as cryptorchidism ( Kaur et al, 2020 ; Boyle et al, 2021 ; Pennings et al, 2020 ). Similarly, knockout mice for KIF7 died at birth ( Table 2 ), and a boy with acrocallosal syndrome (ACLS) who carries a novel homozygous KIF7 nonsense mutation had unilateral maldescensus testis ( Ibisler et al, 2015 ). These findings suggest that kinesins play a crucial role in human testis development, while it may be difficult to discern their functions from the phenotypes of experimental animal models.…”

Section: Kinesins In Human Male Reproductionmentioning

confidence: 99%

Kinesins in Mammalian Spermatogenesis and Germ Cell Transport

Yao

Han

et al. 2022

Front. Cell Dev. Biol.

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In mammalian testes, the apical cytoplasm of each Sertoli cell holds up to several dozens of germ cells, especially spermatids that are transported up and down the seminiferous epithelium. The blood-testis barrier (BTB) established by neighboring Sertoli cells in the basal compartment restructures on a regular basis to allow preleptotene/leptotene spermatocytes to pass through. The timely transfer of germ cells and other cellular organelles such as residual bodies, phagosomes, and lysosomes across the epithelium to facilitate spermatogenesis is important and requires the microtubule-based cytoskeleton in Sertoli cells. Kinesins, a superfamily of the microtubule-dependent motor proteins, are abundantly and preferentially expressed in the testis, but their functions are poorly understood. This review summarizes recent findings on kinesins in mammalian spermatogenesis, highlighting their potential role in germ cell traversing through the BTB and the remodeling of Sertoli cell-spermatid junctions to advance spermatid transport. The possibility of kinesins acting as a mediator and/or synchronizer for cell cycle progression, germ cell transit, and junctional rearrangement and turnover is also discussed. We mostly cover findings in rodents, but we also make special remarks regarding humans. We anticipate that this information will provide a framework for future research in the field.

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Novel <b><i>KIF7</i></b> Mutation in a Tunisian Boy with Acrocallosal Syndrome: Case Report and Review of the Literature

Cited by 17 publications

References 29 publications

Corpus Callosum Agenesis: An Insight into the Etiology and Spectrum of Symptoms

Corpus Callosum Agenesis: An Insight into the Etiology and Spectrum of Symptoms

The deubiquitinating enzyme Usp14 controls ciliogenesis and Hedgehog signaling

Kinesins in Mammalian Spermatogenesis and Germ Cell Transport

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