Dataset Information

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

ABSTRACT: Dysregulated endoplasmic reticulum stress and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) are associated with pancreatic β-cell failure and diabetes. Here, we report the first homozygous mutation in the PPP1R15B gene (also known as constitutive repressor of eIF2α phosphorylation [CReP]) 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. The R658C mutation in PPP1R15B affects a conserved amino acid within the domain important for protein phosphatase 1 (PP1) binding. The R658C mutation decreases PP1 binding and eIF2α dephosphorylation and results in β-cell apoptosis. Our findings support the concept that dysregulated eIF2α phosphorylation, whether decreased by mutation of the kinase (EIF2AK3) in Wolcott-Rallison syndrome or increased by mutation of the phosphatase (PPP1R15B), is deleterious to β-cells and other secretory tissues, resulting in diabetes associated with multisystem abnormalities.

SUBMITTER: Abdulkarim B

PROVIDER: S-EPMC4713904 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Abdulkarim Baroj B Nicolino Marc M Igoillo-Esteve Mariana M Daures Mathilde M Romero Sophie S Philippi Anne A Senée Valérie V Lopes Miguel M Cunha Daniel A DA Harding Heather P HP Derbois Céline C Bendelac Nathalie N Hattersley Andrew T AT Eizirik Décio L DL Ron David D Cnop Miriam M Julier Cécile C

Diabetes 20150709 11

Dysregulated endoplasmic reticulum stress and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) are associated with pancreatic β-cell failure and diabetes. Here, we report the first homozygous mutation in the PPP1R15B gene (also known as constitutive repressor of eIF2α phosphorylation [CReP]) 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 micro ...[more]

PMID: 26159176

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Similar Datasets

Homozygous mutation in the eukaryotic translation initiation factor 2alpha phosphatase gene, PPP1R15B, is associated with severe microcephaly, short stature and intellectual disability.
| S-EPMC4614701 | biostudies-literature

CRIPT exonic deletion and a novel missense mutation in a female with short stature, dysmorphic features, microcephaly, and pigmentary abnormalities.
| S-EPMC5725961 | biostudies-literature

A homozygous IER3IP1 mutation causes microcephaly with simplified gyral pattern, epilepsy, and permanent neonatal diabetes syndrome (MEDS).
| S-EPMC3477270 | biostudies-literature

High Incidence of Noonan Syndrome Features Including Short Stature and Pulmonic Stenosis in Patients carrying NF1 Missense Mutations Affecting p.Arg1809: Genotype-Phenotype Correlation.
| S-EPMC5049609 | biostudies-literature

Monogenic causes of familial short stature.
| S-EPMC11693446 | biostudies-literature

PUF60 variants cause a syndrome of ID, short stature, microcephaly, coloboma, craniofacial, cardiac, renal and spinal features.
| S-EPMC5392357 | biostudies-literature

MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency in humans.
| S-EPMC3287227 | biostudies-literature

A syndrome of short stature, microcephaly and speech delay is associated with duplications reciprocal to the common Sotos syndrome deletion.
| S-EPMC2987195 | biostudies-literature

Familial Xp11.22 microdeletion including SHROOM4 and CLCN5 is associated with intellectual disability, short stature, microcephaly and Dent disease: a case report.
| S-EPMC6327553 | biostudies-literature

<i>MAFA</i> missense mutation causes familial insulinomatosis and diabetes mellitus.
| S-EPMC5798333 | biostudies-literature