A new autosomal dominant eye and lung syndrome linked to mutations in TIMP3 gene
Résumé
To revisit the autosomal dominant Sorsby fundus dystrophy (SFD) as a syndromic condition including late-onset pulmonary disease. We report clinical and imaging data of ten affected individuals from 2 unrelated families with SFD and carrying heterozygous TIMP3 mutations (c.572A > G, p.Y191C, exon 5, in family 1 and c.113C > G, p.S38C, exon 1, in family 2). In family 1, all SFD patients older than 50 (two generations) had also a severe emphysema, despite no history of smoking or asthma. In the preceding generation, the mother died of pulmonary emphysema and she was blind after the age of 50. Her two great-grandsons (<20 years), had abnormal Bruch Membrane thickness, a sign of eye disease. In family 2, eye and lung diseases were also associated in two generations, both occurred later, and lung disease was moderate (bronchiectasis). This is the first report of a syndromic SFD in line with the mouse model uncovering the role of TIMP3 in human lung morphogenesis and functions. The TIMP3 gene should be screened in familial pulmonary diseases with bronchiectasis, associated with a medical history of visual loss. In addition, SFD patients should be advised to avoid tobacco consumption, to practice sports, and to undergo regular pulmonary examinations.
Mots clés
Mesh:Lung/pathology
Mesh:Secondary
Mesh:Male
Mesh:Base Sequence
Mesh:Aged
Mesh:Protein Structure
Mesh:Tomography
Mesh:X-Ray Computed
Mesh:Pedigree
Mesh:Tissue Inhibitor of Metalloproteinase-3/chemistry
Mesh:Tissue Inhibitor of Metalloproteinase-3/genetics*
Mesh:Macular Degeneration/diagnostic imaging
Mesh:Family
Mesh:Female
Mesh:Genetic Predisposition to Disease*
Mesh:Fundus Oculi
Mesh:Macular Degeneration/genetics*
Mesh:Mutation
Mesh:Humans
Mesh:Middle Aged
Domaines
Sciences du Vivant [q-bio]
Origine : Fichiers éditeurs autorisés sur une archive ouverte
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