Marfan syndrome with neonatal progeroid syndrome‐like lipodystrophy associated with a novel frameshift mutation at the 3′ terminus of the FBN1‐gene

  title={Marfan syndrome with neonatal progeroid syndrome‐like lipodystrophy associated with a novel frameshift mutation at the 3′ terminus of the FBN1‐gene},
  author={Luitgard Graul-Neumann and Tina Kienitz and Peter N. Robinson and Sevjidmaa Baasanjav and Benjamin Karow and G. Gillessen‐kaesbach and Raimund Fahsold and Hartmut Schmidt and Katrin Hoffmann and Eberhard Passarge},
  journal={American Journal of Medical Genetics Part A},
We report on a 25-year-old woman with pronounced generalized lipodystrophy and a progeroid aspect since birth, who also had Marfan syndrome (MFS; fulfilling the Ghent criteria) with mild skeletal features, dilated aortic bulb, dural ectasia, bilateral subluxation of the lens, and severe myopia in addition to the severe generalized lipodystrophy. [] Key Result Mutation analysis in the gene encoding fibrillin 1 (FBN1) revealed a novel de novo heterozygous deletion, c.8155_8156del2 in exon 64.

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

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.

Progeroid facial features and lipodystrophy associated with a novel splice site mutation in the final intron of the FBN1 gene

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 congenital lipodystrophy and a progeroid appearance: Mutation in the penultimate exon of FBN1 causing a recognizable phenotype

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.

Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit

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.

A synonymous variant contributes to a rare Wiedemann-Rautenstrauch syndrome complicated with mild anemia via affecting pre-mRNA splicing

Network analysis showed that POLR3A and FANCA could be STRINGed, indicating both proteins might collaborate for some unknown functions, which would broaden the knowledge for clinicians and genetic counselors and remind them to interpret those synonymous or predicted “benign” variants more carefully.

Analyses of LMNA-negative juvenile progeroid cases confirms biallelic POLR3A mutations in Wiedemann–Rautenstrauch-like syndrome and expands the phenotypic spectrum of PYCR1 mutations

It is suggested that POLR3A mutations are causal for a portion of under-diagnosed early-onset segmental progeroid syndromes, and the clinical spectrum associated with PYCR1 mutations is expanded by showing that they can somewhat resemble HGPS in the first year of life.

A progeroid syndrome with neonatal presentation and long survival maps to 19p13.3p13.2.

A Palestinian family with three affected individuals exhibiting progeroid syndrome characterized by intrauterine growth retardation, a progeroids appearance, failure to thrive, short stature, and hypotonia is reported, anticipated to open the way for the identification of the molecular causes underlying this syndrome.



Nuclear lamin A/C R482Q mutation in canadian kindreds with Dunnigan-type familial partial lipodystrophy.

DNA sequencing of LMNA in five Canadian FPLD probands indicated that each had a novel missense mutation, R482Q, which co-segregated with the F PLD phenotype and was absent from 2000 normal alleles, which suggests that LMNA mutations could underlie other diseases characterized by tissue type- and anatomical site-specific cellular degeneration.

Mutations of FBN1 and genotype–phenotype correlations in Marfan syndrome and related fibrillinopathies

An overview of mutations found in Marfan syndrome and related disorders is provided and potential genotype–phenotype correlations in MFS are discussed to discuss potential genotypes–phenotypes correlations.

Fatal Cardiac Arrhythmia and Long-QT Syndrome in a New Form of Congenital Generalized Lipodystrophy with Muscle Rippling (CGL4) Due to PTRF-CAVIN Mutations

PTRF-CAVIN deficiency presents the phenotypic spectrum caused by a quintessential lack of functional caveolae, and is essential for Caveolae biogenesis.

Genetic basis of congenital generalized lipodystrophy

Several distinct mechanisms can lead to extreme lack of adipose tissue in humans and cause CGL, and high expression of AGPAT2 mRNA in adiposa tissue compared to other isoforms suggests that the mutations might affect the adipose tissues the most.

Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene

Fibrillin is implicate as the protein defective in patients with the Marfan syndrome and a de novo missense mutation in the fibrillin gene is described in two patients with sporadic disease.

Genetic and phenotypic heterogeneity in patients with mandibuloacral dysplasia-associated lipodystrophy.

Mandibuloacral dysplasia (MAD) is a phenotypically heterogeneous, rare autosomal recessive disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of cranial

Gene and phenotype analysis of congenital generalized lipodystrophy in Japanese: a novel homozygous nonsense mutation in seipin gene.

This is the first report on gene and phenotype analysis of CGL in Japanese and identifies a novel nonsense mutation of seipin at codon 275 (R275X), suggesting that AGPAT2 is a minor causative gene, if any, for C GL in Japanese.

Clinical and Molecular Study of 320 Children With Marfan Syndrome and Related Type I Fibrillinopathies in a Series of 1009 Probands With Pathogenic FBN1 Mutations

It is confirmed that the majority of clinical manifestations of Marfan syndrome increase with age, which emphasizes the poor applicability of the international criteria to this diagnosis in childhood and the need for follow-up monitoring in cases of clinical suspicion of Mar fan syndrome.

Pathogenic FBN1 mutations in 146 adults not meeting clinical diagnostic criteria for Marfan syndrome: Further delineation of type 1 fibrillinopathies and focus on patients with an isolated major criterion

It is concluded that patients with FBN1 mutation and only one major clinical criterion or with only minor clinical criteria of one or more organ system do exist but represent only 5% of the adult cohort.