RGD Reference Report - Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis. - Rat Genome Database

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Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis.

Authors: Kappanayil, Mahesh  Nampoothiri, Sheela  Kannan, Rajesh  Renard, Marjolijn  Coucke, Paul  Malfait, Fransiska  Menon, Swapna  Ravindran, Hiran K  Kurup, Renu  Faiyaz-Ul-Haque, Muhammad  Kumar, Krishna  De Paepe, Anne 
Citation: Kappanayil M, etal., Orphanet J Rare Dis. 2012 Sep 3;7:61. doi: 10.1186/1750-1172-7-61.
RGD ID: 42722010
Pubmed: PMID:22943132   (View Abstract at PubMed)
PMCID: PMC3598868   (View Article at PubMed Central)
DOI: DOI:10.1186/1750-1172-7-61   (Journal Full-text)


BACKGROUND: Vascular elasticity is crucial for maintaining hemodynamics. Molecular mechanisms involved in human elastogenesis are incompletely understood. We describe a syndrome of lethal arteriopathy associated with a novel, identical mutation in the fibulin 4 gene (FBLN4) in a unique cohort of infants from South India.
METHODS: Clinical characteristics, cardiovascular findings, outcomes and molecular genetics of twenty-two infants from a distinct population subgroup, presenting with characteristic arterial dilatation and tortuosity during the period August 2004 to June 2011 were studied.
RESULTS: Patients (11 males, 11 females) presented at median age of 1.5 months, belonging to unrelated families from identical ethno-geographical background; eight had a history of consanguinity. Cardiovascular features included aneurysmal dilatation, elongation, tortuosity and narrowing of the aorta, pulmonary artery and their branches. The phenotype included a variable combination of cutis laxa (52%), long philtrum-thin vermillion (90%), micrognathia (43%), hypertelorism (57%), prominent eyes (43%), sagging cheeks (43%), long slender digits (48%), and visible arterial pulsations (38%). Genetic studies revealed an identical c.608A > C (p. Asp203Ala) mutation in exon 7 of the FBLN4 gene in all 22 patients, homozygous in 21, and compound heterozygous in one patient with a p. Arg227Cys mutation in the same conserved cbEGF sequence. Homozygosity was lethal (17/21 died, median age 4 months). Isthmic hypoplasia (n = 9) correlated with early death (<=4 months).
CONCLUSIONS: A lethal, genetic disorder characterized by severe deformation of elastic arteries, was linked to novel mutations in the FBLN4 gene. While describing a hitherto unreported syndrome in this population subgroup, this study emphasizes the critical role of fibulin-4 in human elastogenesis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
EFEMP2Humanarterial tortuosity syndrome  IAGP DNA:missense mutation:CDS:p.D203A (human)RGD 
Efemp2Ratarterial tortuosity syndrome  ISOEFEMP2 (Homo sapiens)DNA:missense mutation:CDS:p.D203A (human)RGD 
Efemp2Mousearterial tortuosity syndrome  ISOEFEMP2 (Homo sapiens)DNA:missense mutation:CDS:p.D203A (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Efemp2  (EGF containing fibulin extracellular matrix protein 2)

Genes (Mus musculus)
Efemp2  (epidermal growth factor-containing fibulin-like extracellular matrix protein 2)

Genes (Homo sapiens)
EFEMP2  (EGF containing fibulin extracellular matrix protein 2)


Additional Information