Dyskeratosis Congenita Associated with Elevated Fetal Hemoglobin, X‐Linked Ocular Albinism, and Juvenile‐Onset Diabetes Mellitus

Reichel, Martin; Grix, Arthur; Isseroff, R. Rivkah

doi:10.1111/j.1525-1470.1992.tb01223.x

Cited by 21 publications

(9 citation statements)

References 23 publications

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“…To address whether telomere length contributes to disease in humans, we asked whether patients with DC might be at risk for developing diabetes. We found several published case reports that have incidentally reported on individuals who carried the diagnosis of DC and who had impaired glucose homeostasis [28], [29], [30]. These individuals were diagnosed with glucose intolerance or diabetes at 20 months, 21, 22 and 50 years of age.…”

Section: Resultsmentioning

confidence: 99%

Short Telomeres Compromise β-Cell Signaling and Survival

Guo

Parry²,

Li³

et al. 2011

PLoS ONE

101

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The genetic factors that underlie the increasing incidence of diabetes with age are poorly understood. We examined whether telomere length, which is inherited and known to shorten with age, plays a role in the age-dependent increased incidence of diabetes. We show that in mice with short telomeres, insulin secretion is impaired and leads to glucose intolerance despite the presence of an intact β-cell mass. In ex vivo studies, short telomeres induced cell-autonomous defects in β-cells including reduced mitochondrial membrane hyperpolarization and Ca2+ influx which limited insulin release. To examine the mechanism, we looked for evidence of apoptosis but found no baseline increase in β-cells with short telomeres. However, there was evidence of all the hallmarks of senescence including slower proliferation of β-cells and accumulation of p16INK4a. Specifically, we identified gene expression changes in pathways which are essential for Ca2+-mediated exocytosis. We also show that telomere length is additive to the damaging effect of endoplasmic reticulum stress which occurs in the late stages of type 2 diabetes. This additive effect manifests as more severe hyperglycemia in Akita mice with short telomeres which had a profound loss of β-cell mass and increased β-cell apoptosis. Our data indicate that short telomeres can affect β-cell metabolism even in the presence of intact β-cell number, thus identifying a novel mechanism of telomere-mediated disease. They implicate telomere length as a determinant of β-cell function and diabetes pathogenesis.

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Section: Resultsmentioning

confidence: 99%

Short Telomeres Compromise β-Cell Signaling and Survival

Guo

Parry²,

Li³

et al. 2011

PLoS ONE

101

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“…So far, a total of eight patients have been reported with biopsy-proven pulmonary fibrosis [13]. Other reported pulmonary manifestations of DC include asthma, hepatopulmonary syndrome, pulmonary microvasculature abnormalities, bronchiectasis, fibrocystic dysplasia, Pneumocystis jiroveci pneumonia and chronic pneumonitis [6]-[9]. …”

Section: Discussionmentioning

confidence: 99%

“…A wide spectrum of respiratory manifestations has been reported, including asthma, pulmonary fibrosis, hepatopulmonary syndrome, pulmonary microvasculature abnormalities, bronchiectasis, fibrocystic dysplasia, Pneumocystis jiroveci pneumonia and chronic pneumonitis [6]-[9]. In this article, we describe an unusual case of fatal bilateral spontaneous pneumothoraces in a woman with DC.…”

Section: Introductionmentioning

confidence: 99%

Fatal bilateral pneumothoraces complicating dyskeratosis congenita: a case report

et al. 2009

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IntroductionDyskeratosis congenita is a rare genodermatosis, characterized by a triad of reticular skin pigmentation, nail dystrophy and leukoplakia of mucous membranes. It is also associated with a variety of non-cutaneous abnormalities such as bone marrow failure, malignancy and pulmonary complications. Among its wide range of clinical manifestations, fatal pneumothorax has rarely been reported.Case presentationWe report the case of a 31-year-old Lebanese woman with dyskeratosis congenita who succumbed to devastating bilateral pneumothoraces.ConclusionCareful surveillance of patients with dyskeratosis congenita is required as incipient respiratory failure due to pneumothorax may be successfully treated if detected at an early stage.

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“…Pulmonary disorders such as asthma,14 Pneumocystis carinii pneumonia,12 hepatopulmonary syndrome of Rodriguez-Roisin and Krowka,6 as well as various pulmonary infections (I Dokal, personal communication) have been reported in patients with DC. However, they may present with restrictive pulmonary disease.…”

Section: Discussionmentioning

confidence: 99%

X-linked dyskeratosis congenita: restrictive pulmonary disease and a novel mutation

Safa

2001

Thorax

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Dyskeratosis congenita (DC) is a rare inherited multisystem disorder characterised by lesions of the skin and appendages. Bone marrow failure occurs in 80% of patients. The gene for the X-linked form of DC has been identified on Xq28 and designated as DKC1. Pulmonary manifestations have rarely been reported. It is not known whether there is a respiratory disease peculiar to these patients and, if so, whether it is associated with a specific genetic mutation. A 40 year old Egyptian man with pulmonary disease and his symptom free 35 year old brother both presented with mucocutaneous lesions characteristic of DC. In the older brother chest imaging revealed generalised intralobular interstitial thickening and honeycombing. Pulmonary function tests showed a restrictive pattern. Open lung biopsy specimens of lung tissue showed various degrees of fibrosis consistent with usual interstitial pneumonia of chronic idiopathic pulmonary fibrosis. The younger brother was free of pulmonary lesions. Both had a novel missense mutation 5C→T in exon 1 of the DKC1 gene. It is concluded that pulmonary disease in DC may be underestimated, possibly because most patients die at an early age of bone marrow failure. No relationship between genotype and phenotype could be established in the patients studied. The genetic diagnosis of DC is now available, which may enable it to be diagnosed in patients with restrictive pulmonary disease and minimal cutaneous signs. (Thorax 2001;56:891-894)

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Dyskeratosis Congenita Associated with Elevated Fetal Hemoglobin, X‐Linked Ocular Albinism, and Juvenile‐Onset Diabetes Mellitus

Cited by 21 publications

References 23 publications

Short Telomeres Compromise β-Cell Signaling and Survival

Short Telomeres Compromise β-Cell Signaling and Survival

Fatal bilateral pneumothoraces complicating dyskeratosis congenita: a case report

X-linked dyskeratosis congenita: restrictive pulmonary disease and a novel mutation

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