De novo heterozygous FBN1 mutations in the extreme C‐terminal region cause progeroid fibrillinopathy

@article{Garg2014DeNH,
  title={De novo heterozygous FBN1 mutations in the extreme C‐terminal region cause progeroid fibrillinopathy},
  author={Abhimanyu Garg and Chao Xing},
  journal={American Journal of Medical Genetics Part A},
  year={2014},
  volume={164},
  pages={1341 - 1345}
}
  • A. Garg, C. Xing
  • Published 1 May 2014
  • Medicine, Biology
  • American Journal of Medical Genetics Part A
De Novo Heterozygous FBN1 Mutations in the Extreme C-Terminal Region Cause Progeroid Fibrillinopathy Abhimanyu Garg,* and Chao Xing Division of Nutrition and Metabolic Diseases, Department of Internal Medicine and the Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas Department of Clinical Sciences and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas 
Marfanoid–progeroid–lipodystrophy syndrome: a newly recognized fibrillinopathy
TLDR
It is suggested that this previously unknown genotype/phenotype relationship constitutes a new fibrillinopathy for which the name marfanoid–progeroid–lipodystrophy syndrome would be appropriate.
Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit
TLDR
A novel genetically engineered rabbit model ofMPL syndrome, generated by CRISPR/Cas9-mediated mutation of FBN1, mimics the histopathological changes and functional defects of MPL syndrome seen in the clinic.
Genetic and molecular mechanism for distinct clinical phenotypes conveyed by allelic truncating mutations implicated in FBN1
TLDR
Overall, this study provides direct evidence that a dominant negative interaction of FBN1 potentially explains the distinct clinical phenotype in MPLS patients through genetic and functional analysis of the first Chinese patient with MPLS.
Wiedemann–Rautenstrauch syndrome in an Indian patient with biallelic pathogenic variants in POLR3A
TLDR
An 18 months old male child with biallelic c.2005C>T p.(Arg669Ter) and c.1771‐7C>G variant in heterozygous state identified by exome sequencing in POLR3A leading to WRS phenotype is described.
Congenital generalized lipodystrophies—new insights into metabolic dysfunction
TLDR
Aside from conventional therapy for hyperlipidaemia and diabetes mellitus, metreleptin replacement therapy can dramatically improve metabolic complications in patients with CGL.
Wiedemann–Rautenstrauch syndrome: A phenotype analysis
TLDR
Compared the WRS phenotype with characteristics of conditions known to be caused by autosomal recessively inherited POLR3A mutations, there are major differences but there are also similarities in phenotype, which sustain the suggestion that the syndrome can be cause by disturbed POLR 3A functioning.
Fibrillin-1 and fibrillin-1-derived asprosin in adipose tissue function and metabolic disorders
TLDR
Understanding the dynamic role of fibrillin-1 in the adipose tissue milieu and of circulating asprosin in the body can provide novel mechanistic insights into how fibrisin-1 may contribute to metabolic syndrome, which could lead to new management regimens of patients with metabolic disease.
Lipodystrophy Syndromes.
...
...

References

SHOWING 1-10 OF 18 REFERENCES
The fibrillin-1 gene: unlocking new therapeutic pathways in cardiovascular disease
TLDR
Although an FBN-1 mutation does not guarantee the diagnosis of Marfan syndrome it is clear however that FBn-1 mutations independently confer additional risk for many of the cardiovascular complications classically associated with the disease.
Further evidence for a marfanoid syndrome with neonatal progeroid features and severe generalized lipodystrophy due to frameshift mutations near the 3′ end of the FBN1 gene
TLDR
A 20‐year‐old man who presented in infancy with severe generalized lipodystrophy with a progeroid appearance and some Marfanoid features is reported on, showing him to have a novel heterozygous, de novo, c.8156_8175del, p.Lys2719ThrfsX12, frameshift mutation in exon 64 of his FBN1 gene.
Marfan syndrome with neonatal progeroid syndrome‐like lipodystrophy associated with a novel frameshift mutation at the 3′ terminus of the FBN1‐gene
TLDR
A 25‐year‐old woman with pronounced generalized lipodystrophy and a progeroid aspect since birth, who also had Marfan syndrome with mild skeletal features, dilated aortic bulb, dural ectasia, bilateral subluxation of the lens, and severe myopia is reported on.
Cardiovascular manifestations in men and women carrying a FBN1 mutation.
TLDR
The CV risk remains important in patients with an FBN1 gene mutation and is present throughout life, justifying regular aortic monitoring and thorough examination for extra-aortic features and comprehensive pedigree investigation.
Progeroid facial features and lipodystrophy associated with a novel splice site mutation in the final intron of the FBN1 gene
TLDR
It is suggested a specific clinical entity characterized by progeroid facial features, lipodystrophy, and at least some clinical signs of Marfan syndrome is associated with a subset of mutations located at the 3′ end of FBN1.
Severe complications in a child with achondroplasia and two FGFR3 mutations on the same allele
TLDR
To the authors' knowledge, this is the first report in the literature on an achondroplasia patient with two FGFR3 mutations on the same allele, and it appears to have occurred de novo.
A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogene.
TLDR
A novel case of multiple endocrine neoplasia type 2A (MEN 2A) associated with two mutations of the protooncogene RET, present on the same RET allele and associated with a calcitonin-producing pheochromocytoma is reported.
Novel p.C620L RET Mutation Detected in a Patient with Medullary Thyroid Carcinoma
TLDR
The early age of onset for medullary thyroid carcinoma and the presence of lymph node metastasis in this patient suggests individuals with the p.C620L mutation should be treated and screened as Multiple Endocrine Neoplasia type 2 patients with other RET codon 620 mutations (American Thyroid Association risk level B).
Severe congenital lipodystrophy and a progeroid appearance: Mutation in the penultimate exon of FBN1 causing a recognizable phenotype
TLDR
It is proposed that this marfanoid entity comprised of congenital lipodystrophy, a neonatal progeroid appearance, and a peculiar growth profile and caused by rare mutations in the penultimate exon of FBN1, be newly referred to as marfanoids–progeroid syndrome.
Novel p . C 620 L RET Mutation Detected in a Patient with Medullary Thyroid Carcinoma
TLDR
The early age of onset for medullary thyroid carcinoma and the presence of lymph node metastasis in this patient suggests individuals with the p.C620L mutation should be treated and screened as Multiple Endocrine Neoplasia type 2 patients with other RET codon 620 mutations (American Thyroid Association risk level B).
...
...