Hutchinson–Gilford progeria syndrome: clinical findings in three patients carrying the G608G mutation in LMNA and review of the literature

@article{MazereeuwHautier2007HutchinsonGilfordPS,
  title={Hutchinson–Gilford progeria syndrome: clinical findings in three patients carrying the G608G mutation in LMNA and review of the literature},
  author={Juliette Mazereeuw-Hautier and Louise C Wilson and Sara Mohammed and David M Smallwood and Sue Shackleton and D. J. Atherton and John I. Harper},
  journal={British Journal of Dermatology},
  year={2007},
  volume={156}
}
Background  Hutchinson–Gilford progeria syndrome (HGPS) is a rare premature ageing disorder that belongs to a group of conditions called laminopathies which affect nuclear lamins. Classical and atypical forms of HGPS have been reported and there are clinical overlaps with mandibulo‐acral dysplasia and restrictive dermopathy. To date, mutations in two genes, LMNA and ZMPSTE24, have been found in patients with HGPS. The p.G608G LMNA mutation is the most commonly reported mutation. Correlations… 
Molecular ageing in progeroid syndromes: Hutchinson-Gilford progeria syndrome as a model
TLDR
A comprehensive literature review of the clinical features and genetic mutations and mechanisms of Hutchinson-Gilford progeria syndrome shows the necessity of a more detailed clinical identification and the need for more studies on the pharmacologic and pharmacogenomic approach to this syndrome.
Skin signs as early manifestations of Hutchinson-Gilford progeria syndrome
TLDR
The case of a 7-month-old baby with HGPS is reported, a rare, sporadic, autosomal dominant genetic disorder with phenotypic features of accelerated ageing due to a mutation of the lamin A (LMNA) gene.
Hutchinson–Gilford Progeria Syndrome Caused by an LMNA Mutation: A Case Report
TLDR
A 6‐year‐old boy who was born at full term but presented with scleroderma‐like appearance at 1 month of age and gradually developed clinical manifestations of progeria develops characteristic facial features of prominent eyes, scalp, and leg veins.
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.
Phenotype and course of Hutchinson-Gilford progeria syndrome.
TLDR
Clinical investigations confirmed sclerotic skin, joint contractures, bone abnormalities, alopecia, and growth impairment in all 15 patients; cardiovascular and central nervous system sequelae were also documented.
The clinical characteristics of Asian patients with classical-type Hutchinson–Gilford progeria syndrome
TLDR
To circumvent or minimalize severe vascular complication, an early diagnosis, careful observation and, promisingly, new intervention with farnesylation inhibitors may improve the prognosis of classical HGPS patients.
Molecular studies of Hutchinson-Gilford progeria syndrome
TLDR
To increase the understanding of the molecular mechanisms underlying progeria, to see if there is any possibility of disease reversal and to develop a specific method for analyzing LMNA transcripts during normal and in vitro aging, an inducible tissuespecific transgenic mouse model of HGPS is developed.
Clinical and radiographic features of Hutchinson-Gilford progeria syndrome: A case report.
TLDR
A case report of an 11-year-old boy with classical features of HGPS, which was caused by a de novo germ-line mutation (C1824T, G608G) in exon 11 of the LMNA gene.
» HUTCHINSON-GILFORD PROGERIA SYNDROME (HGPS) WITH MITOCHONDRIAL DNA (MTDNA) HV1 CONTROL REGION MUTATIONS
TLDR
On the first ever Progeria male patient identified in Bangladesh, the mitochondrial DNA genome is analyzed by direct sequencing with AB3130 Genetic Analyzer and some novel mtDNA anomalies are reported, none of which are observed in patient's maternal relatives.
...
...

References

SHOWING 1-10 OF 23 REFERENCES
p.S143F mutation in lamin A/C: A new phenotype combining myopathy and progeria
TLDR
A young girl with a phenotype combining early‐onset myopathy and a progeria is reported, the first report of a patient combining features of these two phenotypes because of a single mutation in LMNA.
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.
Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes
TLDR
Children with HGPS usually appear normal in early infancy, but at about six months of age begin to experience profound growth delay, and the skin acquires an abnormally aged appear- ance with prominent veins.
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.
Hutchinson–Gilford progeria syndrome: Review of the phenotype
  • R. Hennekam
  • Medicine
    American journal of medical genetics. Part A
  • 2006
TLDR
Patients can be subdivided in patients with classical HGPS, which follows an autosomal dominant pattern of inheritance, all cases representing spontaneous mutations, and in non‐classical progeria, in whom growth can be less retarded, scalp hair remains present for a longer time, lipodystrophy is more slowly progressive, osteolysis is more expressed except in the face, and survival well into adulthood.
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.
Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome
TLDR
Evidence of mutations in lamin A (LMNA) as the cause of Hutchinson–Gilford progeria syndrome is presented, and the discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing.
Lamin A Truncation in Hutchinson-Gilford Progeria
TLDR
HGPS is an exceedingly rare but typical progeria, clinically characterized by postnatal growth retardation, midface hypoplasia, micrognathia, premature atherosclerosis, absence of subcutaneous fat, and others.
Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C.
TLDR
Pat skin fibroblasts showed nuclei that presented abnormal lamin A/C distribution and a dysmorphic envelope, thus demonstrating the pathogenic effect of the R527H LMNA mutation, which was shared by all affected patients.
...
...