Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome

@article{Eriksson2003RecurrentDN,
  title={Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome},
  author={Maria Eriksson and William Ted Brown and Leslie B Gordon and Michael W. Glynn and Joel Singer and Laura J. Scott and Michael R. Erdos and Christiane M. Robbins and Tracy Y. Moses and Peter Berglund and Amalia S Dutra and Evgenia Pak and Sandra Durkin and Antonei B Csoka and Michael Boehnke and Thomas W. Glover and Francis S. Collins},
  journal={Nature},
  year={2003},
  volume={423},
  pages={293-298}
}
Hutchinson–Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by features reminiscent of marked premature ageing. [...] Key Result Sequencing of LMNA, located in this interval and previously implicated in several other heritable disorders, revealed that 18 out of 20 classical cases of HGPS harboured an identical de novo (that is, newly arisen and not inherited) single-base substitution, G608G(GGC > GGT), within exon 11.Expand
Paternal origin of LMNA mutations in Hutchinson–Gilford progeria
TLDR
It is shown that G608G mutation responsible for the majority of cases of HGPS arises in the paternal germline, and an advanced paternal age in the fathers of affected individuals is confirmed. Expand
Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome
TLDR
It is reported that heterozygous, recurrent de novo point mutations in the lamin A/C gene, a component of the filamentous meshwork of the nuclear lamina, caused Hutchinson-Gilford progeria syndrome. Expand
Hutchinson–Gilford progeria syndrome
TLDR
The discovery of the HGPS mutations brings the total number of diseases caused by mutant Lmna to nine, underscoring the astonishing spectrum of laminopathies. Expand
Compound heterozygous ZMPSTE24 mutations reduce prelamin A processing and result in a severe progeroid phenotype
TLDR
A genetic cause has now been implicated following the identification of de novo heterozygous mutations in the LMNA gene in the majority of HGPS patients, which is an extremely rare but devastating disorder that mimics premature aging. Expand
Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes
TLDR
Two patients with extraordinarily severe forms of progeria caused by unusual mutations in LMNA are presented, and farnesyltransferase inhibitors may prove to be useful even when progerin expression levels are higher than those in typical HGPS patients. Expand
Compound heterozygosity for mutations in LMNA causes a progeria syndrome without prelamin A accumulation.
TLDR
A critical role for the C-terminal globular lamin A/C region in nuclear structure is suggested and support a major contribution of abnormal assembly to the progeroid phenotype is supported. Expand
An inherited LMNA gene mutation in atypical Progeria syndrome
TLDR
The observation of a non‐consanguineous Moroccan patient presenting with atypical progeria is discussed and the molecular studies showed the heterozygous mutation c.412G>A (p.Gly608Gly) of the LMNA gene, previously reported as a de novo mutation, was inherited from the apparently healthy father who showed a somatic cell mosaicism. Expand
RISK FACTORS, PREVALENCE AND DIAGNOSIS OF HUTCHISON GILFORD SYNDROME WITH SPECIAL REFERENCE TO CASE REPORTS
TLDR
There is presently no effective therapy is available for Hutchinson-Gilford progeria syndrome (HGPS), but, it is essential to monitor carefully cardiovascular and cerebrovascular disease. Expand
Hutchinson-Gilford progeria syndrome
TLDR
Recent studies have shown that blocking famesylation of progerin via the use of farnesyltransferase inhibitors can reduce nuclear blebbing and thus HGPS pathogenicity and pharmacological targeting to correct cellular phenotypes associated with HGPS could be utilized in the future for therapeutic intervention. Expand
Le syndrome de hutchinson-gilford (PROGERIA) : analyse clinique et moléculaire chez une patiente d'origine africaine
TLDR
A 12 year-old-girl African patient with HGPS, in whom the p.Gly608Gly heterozygous disease-causing mutation was found, is reported here. Expand
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