A Dominant Mutation in Hexokinase 1 (<i>HK1</i>) Causes Retinitis Pigmentosa

Sullivan, Lori S.; Koboldt, Daniel C.; Bowne, Sara J.; Lang, Steven; Blanton, Susan H.; Cadena, Elizabeth; Avery, Cheryl E.; Lewis, Richard A.; Webb‐Jones, Kaylie; Wheaton, Dianna K.; Birch, David G.; Coussa, Razek Georges; Ren, Haitao; López, Irma; Chakarova, Christina; Koenekoop, Robert K.; Garcia, Charles A.; Fulton, Robert S.; Wilson, Richard K.; Weinstock, George M.; Daiger, Stephen P.

doi:10.1167/iovs.14-15419

Cited by 45 publications

(49 citation statements)

References 53 publications

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“…We were able to detect putative disease-causing mutations in 14 out of the 29 probands analysed. This resulted in a clinically relevant genetic diagnosis ratio of 48.28%, which is comparable to values reported previously, ranging from about 24% to 88%6727282930313233. Several factors may be responsible for this wide range of diagnosis ratios reported, including the approach used or the nature of the cohort involved.…”

Section: Discussionsupporting

confidence: 82%

High prevalence of mutations affecting the splicing process in a Spanish cohort with autosomal dominant retinitis pigmentosa

Ezquerra-Inchausti

Barandika

Anasagasti

et al. 2017

Sci Rep

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Retinitis pigmentosa is the most frequent group of inherited retinal dystrophies. It is highly heterogeneous, with more than 80 disease-causing genes 27 of which are known to cause autosomal dominant RP (adRP), having been identified. In this study a total of 29 index cases were ascertained based on a family tree compatible with adRP. A custom panel of 31 adRP genes was analysed by targeted next-generation sequencing using the Ion PGM platform in combination with Sanger sequencing. This allowed us to detect putative disease-causing mutations in 14 out of the 29 (48.28%) families analysed. Remarkably, around 38% of all adRP cases analysed showed mutations affecting the splicing process, mainly due to mutations in genes coding for spliceosome factors (SNRNP200 and PRPF8) but also due to splice-site mutations in RHO. Twelve of the 14 mutations found had been reported previously and two were novel mutations found in PRPF8 in two unrelated patients. In conclusion, our results will lead to more accurate genetic counselling and will contribute to a better characterisation of the disease. In addition, they may have a therapeutic impact in the future given the large number of studies currently underway based on targeted RNA splicing for therapeutic purposes.

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Section: Discussionsupporting

confidence: 82%

High prevalence of mutations affecting the splicing process in a Spanish cohort with autosomal dominant retinitis pigmentosa

Ezquerra-Inchausti

Barandika

Anasagasti

et al. 2017

Sci Rep

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“…However, in some cases the genetic defect is yet to be defined. Recently, a dominant mutation in the gene that encodes HK1 (hexokinase 1, an enzyme that catalyzes the phosphorylation of glucose in the glucolytic pathway) was found to cause RP (Sullivan et al, 2014).…”

Section: Retinitis Pigmentosa (Rp)mentioning

confidence: 99%

Glia–neuron interactions in the mammalian retina

Vecino

Rodríguez

Ruzafa

et al. 2016

Progress in Retinal and Eye Research

615

533

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The mammalian retina provides an excellent opportunity to study glia-neuron interactions and the interactions of glia with blood vessels. Three main types of glial cells are found in the mammalian retina that serve to maintain retinal homeostasis: astrocytes, Müller cells and resident microglia. Müller cells, astrocytes and microglia not only provide structural support but they are also involved in metabolism, the phagocytosis of neuronal debris, the release of certain transmitters and trophic factors and K(+) uptake. Astrocytes are mostly located in the nerve fibre layer and they accompany the blood vessels in the inner nuclear layer. Indeed, like Müller cells, astrocytic processes cover the blood vessels forming the retinal blood barrier and they fulfil a significant role in ion homeostasis. Among other activities, microglia can be stimulated to fulfil a macrophage function, as well as to interact with other glial cells and neurons by secreting growth factors. This review summarizes the main functional relationships between retinal glial cells and neurons, presenting a general picture of the retina recently modified based on experimental observations. The preferential involvement of the distinct glia cells in terms of the activity in the retina is discussed, for example, while Müller cells may serve as progenitors of retinal neurons, astrocytes and microglia are responsible for synaptic pruning. Since different types of glia participate together in certain activities in the retina, it is imperative to explore the order of redundancy and to explore the heterogeneity among these cells. Recent studies revealed the association of glia cell heterogeneity with specific functions. Finally, the neuroprotective effects of glia on photoreceptors and ganglion cells under normal and adverse conditions will also be explored.

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“…Recently, we reported a novel adRP gene, hexokinase 1 (HK1), with a missense mutation in five independently ascertained families (Sullivan et al 2014). This gene, too, was tested in the cohort.…”

Section: Prevalence Of Disease-causing Mutations In Adrp Familiesmentioning

confidence: 99%

“…For example, the rhodopsin Pro23His mutation (13%) and the peripherin 828+3A>T mutation (2%) arose by founder effect, are almost exclusive to the United States, and are found only in Americans of European origin (Dryja et al 1990, 1991; Shankar et al 2004). The hexokinase Glu847Lys mutation also arose from a common ancestor, but the mutation is found in North America and Europe (Sullivan et al 2014). In contrast, the Asp226Asn mutation in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) arose independently on multiple occasions (Sullivan et al 2006a).…”

Section: Prevalence Of Disease-causing Mutations In Adrp Familiesmentioning

confidence: 99%

“…In contrast, the consequences of this mutation are distinct from clinical expression of the several RP1 mutations, which are truly recessive, with unaffected carriers (Khaliq et al 2005; Riazuddin et al 2005). Similarly, in a large adRP family with the HK1 Glu847Lys mutation, a single homozygous individual is significantly more severely affected than heterozygotes (Sullivan et al 2014). These cases may be rare, but because members of large, multigenerational adRP families occasionally live in the same community, this is more likely with adRP than with other dominant diseases.…”

Section: Dominant-recessive Acting Adrp Mutationsmentioning

confidence: 99%

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Genes and Mutations Causing Autosomal Dominant Retinitis Pigmentosa

Daiger

Bowne

Sullivan

2014

Cold Spring Harb Perspect Med

Self Cite

116

140

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Retinitis pigmentosa (RP) has a prevalence of approximately one in 4000; 25%–30% of these cases are autosomal dominant retinitis pigmentosa (adRP). Like other forms of inherited retinal disease, adRP is exceptionally heterogeneous. Mutations in more than 25 genes are known to cause adRP, more than 1000 mutations have been reported in these genes, clinical findings are highly variable, and there is considerable overlap with other types of inherited disease. Currently, it is possible to detect disease-causing mutations in 50%–75% of adRP families in select populations. Genetic diagnosis of adRP has advantages over other forms of RP because segregation of disease in families is a useful tool for identifying and confirming potentially pathogenic variants, but there are disadvantages too. In addition to identifying the cause of disease in the remaining 25% of adRP families, a central challenge is reconciling clinical diagnosis, family history, and molecular findings in patients and families.

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A Dominant Mutation in Hexokinase 1 (HK1) Causes Retinitis Pigmentosa

Cited by 45 publications

References 53 publications

High prevalence of mutations affecting the splicing process in a Spanish cohort with autosomal dominant retinitis pigmentosa

High prevalence of mutations affecting the splicing process in a Spanish cohort with autosomal dominant retinitis pigmentosa

Glia–neuron interactions in the mammalian retina

Genes and Mutations Causing Autosomal Dominant Retinitis Pigmentosa

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