EIF2AK3, encoding translation initiation factor 2-α kinase 3, is mutated in patients with Wolcott-Rallison syndrome

@article{Delepine2000EIF2AK3ET,
  title={EIF2AK3, encoding translation initiation factor 2-$\alpha$ kinase 3, is mutated in patients with Wolcott-Rallison syndrome},
  author={Marcel Delepine and Marc Nicolino and Timothy G Barrett and Mahamadee Golamaully and G. Mark Lathrop and C{\'e}cile Julier},
  journal={Nature Genetics},
  year={2000},
  volume={25},
  pages={406-409}
}
Wolcott-Rallison syndrome (WRS) is a rare, autosomal recessive disorder characterized by permanent neonatal or early infancy insulin-dependent diabetes. Epiphyseal dysplasia, osteoporosis and growth retardation occur at a later age. Other frequent multisystemic manifestations include hepatic and renal dysfunction, mental retardation and cardiovascular abnormalities. On the basis of two consanguineous families, we mapped WRS to a region of less than 3 cM on chromosome 2p12, with maximal evidence… 

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Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene.

It is demonstrated that EIF2AK3 kinase activity is essential for pancreas islet function and bone development in humans, and EIF 2AK3 as a possible target for therapeutic intervention in diabetes is suggested.

Re: EIF2AK3 Mutations in Patients with Wolcott-Rallison Syndrome

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  • 2005
Evidence is provided for the role of EIF2AK# deficiency in Wolcott-Rallison syndrome at the molecular level and for EIF1aK3 kinase activity, which appears to be essential for pancreatic islet cell function and bone development in humans.

Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity.

The patient with no EIF2AK3 involvement did not have any of the other variable clinical manifestations associated with WRS, which supports the idea that the genetic heterogeneity between this variant form of WRS and EIF 2AK3 WRS correlates with some clinical heterogeneity.

A novel splice site indel alteration in the EIF2AK3 gene is responsible for the first cases of Wolcott-Rallison syndrome in Hungary

The novel genetic alteration causing the absence of the EIF2AK3 protein resulted in insufficient handling of severe endoplasmic reticulum stress, leading to liver failure and demise of the patients.

A novel mutation in the EIF2AK3 gene with variable expressivity in two patients with Wolcott–Rallison syndrome

Two cases from different families carrying the same and novel truncating nonsense mutation in the EIF2AK3 gene that encodes the pancreatic eukaryotic initiation factor 2α kinase 3 are reported, illustrating the important role of alternative pathways that could, to some extent, take over or supplement a defective metabolic pathway.

Identification of Two Novel Compound Heterozygous EIF2AK3 Mutations Underlying Wolcott–Rallison Syndrome in a Chinese Family

The identification of the variations and verification of their pathogenicity extended the variation spectrum of EIF2AK3 variations causing Wolcott–Rallison syndrome and enriched valuable information for precise medical intervention for Wolcott-Rallisons syndrome in China.

A novel EIF2AK3 mutation leading to Wolcott-Rallison syndrome in a Chinese child

ETF2AK3 gene mutations can lead to the onset of Wolcott-Rallison syndrome, a rare recessive disorder characterized by early-onset diabetes, skeletal abnormalities, and liver dysfunction, and DNA direct assay techniques were used for gene mutation analysis.

A Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly

The first homozygous mutation in the PPP1R15B gene is reported encoding the regulatory subunit of an eIF2α-specific phosphatase in two siblings affected by a novel syndrome of diabetes of youth with short stature, intellectual disability, and microcephaly.

Wolcott-Rallison syndrome: pathogenic insights into neonatal diabetes from new mutation and expression studies of EIF2AK3

New features of the expression pattern of human EIF2AK3 that offer possible explanations for important clinical features ofThe Wolcott-Rallison syndrome that are not apparent in the transgenic mouse models are demonstrated.

EIF2AK3 novel mutation in a child with early-onset diabetes mellitus, a case report

Screening for genetic mutations in EIF2AK3 is recommended for establishing early diagnosis, providing genetic counselling, and predicting the development of additional clinical features, most importantly hepatic failure.
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