A new autosomal dominant eye and lung syndrome linked to mutations in TIMP3 gene

作者：Meunier Isabelle^*; Bocquet Beatrice; Labesse Gilles; Zeitz Christina; Defoort Dhellemmes Sabine; Lacroux Annie; Mauget Faysse Martine; Drumare Isabelle; Gamez Anne Sophie; Mathieu Cyril; Marquette Virginie; Sagot Lola; Dhaenens Claire Marie; Arndt Carl; Carroll Patrick; Remy Jardin Martine; Cohen Salomon Yves; Sahel Jose Alain; Puech Bernard; Audo Isabelle; Mrejen Sarah; Hamel Christian P

来源：Scientific Reports, 2016, 6(1): 32544.

DOI：10.1038/srep32544

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.

• 出版日期2016-9-7