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Gilford Progeria Syndrome (gilford + progeria_syndrome)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

Microcephalia with mandibular and dental dysplasia in adult Zmpste24-deficient mice

JOURNAL OF ANATOMY, Issue 5 2008
F. De Carlos
Abstract ZMPSTE24 (also called FACE-1) is a zinc-metalloprotease involved in the post-translational processing of prelamin A to mature lamin A, a major component of the nuclear envelope. Mutations in the ZMPSTE24 gene or in that encoding its substrate prelamin A (LMNA) result in a series of human inherited diseases known collectively as laminopathies and showing regional or systemic manifestations (i.e. the Hutchinson,Gilford progeria syndrome). Typically, patients suffering some laminopathies show craniofacial or mandible anomalies, aberrant dentition or facial features characteristic of aged persons. To analyse whether Zmpste24,/, mice reproduce the cranial phenotype observed in humans due to mutations in ZMPSTE24 or LMNA, we conducted a craniometric study based on micro-computer tomography (µCT) images. Furthermore, using simple radiology, µCT, µCT-densitometry and scanning electron microscopy, we analysed the mandible and the teeth from Zmpste24,/, mice. Finally, the structure of the lower incisor was investigated using an H&E technique. The results demonstrate that Zmpste24,/, mice are microcephalic and show mandibular and dental dysplasia affecting only the mandible teeth. In all cases, the lower incisor of mice lacking Zmpste24 was smaller than in control animals, showed cylindrical morphology and a transverse fissure at the incisal edge, and the pulpal cavity was severely reduced. Structurally, the dental layers were normally arranged but cellular layers were disorganized. The inferior molars showed a reduced cusp size. Taken together, these data strongly suggest that Zmpste24,/, mice represent a good model to analyse the craniofacial and teeth malformations characteristic of lamin-related pathologies, and might contribute to a better understanding of the molecular events underlying these diseases. [source]

Homozygous LMNA mutation R527C in atypical Hutchinson,Gilford progeria syndrome: evidence for autosomal recessive inheritance

ACTA PAEDIATRICA, Issue 8 2009
Lili Liang
Abstract Aim:, To describe two Chinese siblings of atypical Hutchinson,Gilford progeria syndrome (HGPS), with genetic diagnosis and special clinical manifestation. Methods:, We screened the LMNA gene in four members of a consanguineous family, in which two children were suffering from atypical HGPS. Besides general HGPS features, such as growth retardation and characteristic appearance, special clinical phenotypes including disorders of digestive system and severe skeletal damages were observed. Results:, Homozygous mutation 1579C>T, which predicts R527C, was identified in the exon 9 of LMNA among the affected siblings. Heterozygous carrier status 1579C>T was detected in both of the asymptomatic parents. Conclusion:, Homozygous mutation R527C in LMNA yields atypical HGPS, and it suggests an autosomal recessive inheritance in this family. [source]

Hutchinson,Gilford progeria syndrome with severe skin calcinosis

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 5 2007
S. Nakamura
Summary We describe a case of Hutchinson,Gilford progeria syndrome (HGPS) with long-term follow-up. A 1-month-old girl with marked sclerodermatous skin changes developed various symptoms of HGPS during follow-up. These included sclerotic skin, pigmentation, skin atrophy with translucent veins, wispy hair and alopecia, nail dystrophy and decreased sweating. Marked skin calcinosis was observed over almost the entire body, a symptom that has apparently been ignored in the literature. At 16 years old, the girl underwent surgery for a skull fracture and subdural haematoma, which was followed by chronic ulceration. Wet dressing with insulin-like growth factor was used with considerable effect. Mutation of the lamin A/C (LMNA) gene mutation, which encodes nuclear lamin A and C, has been reported to be the cause of HGPS. Our case showed the mutation G608G (GGC,GGT), which resulted in a cryptic splice site and consequently in a truncated lamin A/C protein. [source]