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
Autor: | Paul Coucke, Marjolijn Renard, Sheela Nampoothiri, Mahesh Kappanayil, Renu P. Kurup, Krishna Kumar, Hiran K Ravindran, Muhammad Faiyaz-Ul-Haque, Fransiska Malfait, Swapna Menon, Anne De Paepe, Rajesh Kannan |
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Jazyk: | angličtina |
Předmět: |
Male
Pathology Fibulin-4 mutation ELASTIC FIBER Compound heterozygosity PULMONARY Malabar Medicine and Health Sciences Genetics(clinical) Pharmacology (medical) HOMOZYGOSITY Mappila muslims Hypertelorism Genetics (clinical) PHENOTYPIC FEATURES Medicine(all) Extracellular Matrix Proteins Aortic aneurysm ARTERIAL-TORTUOSITY-SYNDROME Genetic disorder General Medicine Anatomy Founder effect Hypoplasia FAMILY CARDIOVASCULAR MANIFESTATIONS Genetic vasculopathy Female medicine.symptom Arterial tortuosity Lethal mutation Arterial tortuosity syndrome medicine.medical_specialty Consanguinity Biology ANEURYSM medicine Humans Vascular Diseases AORTIC-VALVE Research Vascular elasticity Abnormal elastogenesis Infant Newborn Infant medicine.disease Elastic Tissue Connective tissue disorder Fibulin Cardiovascular imaging CUTIS-LAXA Cutis laxa |
Zdroj: | Orphanet Journal of Rare Diseases ORPHANET JOURNAL OF RARE DISEASES |
ISSN: | 1750-1172 |
DOI: | 10.1186/1750-1172-7-61 |
Popis: | 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 ( |
Databáze: | OpenAIRE |
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