A Novel Mutation at the N-Terminal Domain of the Timp3 Gene in Sorsby Fundus Dystrophy

Schoenberger, Scott D.

doi:10.1097/iae.0b013e318263d3b4

Cited by 19 publications

(27 citation statements)

References 24 publications

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“…We found the TIMP3 variation c.113C > G (p.S38C) in exon 1 which has been previously described in SFD24. This variation is considered to be probably damaging by PolyPhen 2 with a score = 1 (http://genetics.bwh.harvard.edu/pph2), damaging according to SIFT with a score = 0 (http://sift.jcvi.org), and to interfere most likely with the function of the protein by the align-GVDG program with a class C65 (http://agvgd.iarc.fr/agvgd_input.php), disease causing for mutation taster with a probability of 0.99 (www.mutationtaster.org), and deleterious for Provean (provean.jcvi.org).…”

Section: Resultssupporting

confidence: 79%

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

Meunier

Bocquet

Labesse

et al. 2016

Sci Rep

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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.

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Section: Resultssupporting

confidence: 79%

“…In addition, the mutation co-segregated with the disease in the family. This mutation has been reported previously in 5 SFD unrelated patients2425.…”

Section: Resultssupporting

confidence: 77%

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

Meunier

Bocquet

Labesse

et al. 2016

Sci Rep

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“…Although in our cohort, this lesion subtype was associated only with TIMP3 mutation c.530A/G, a review of the literature revealed findings strongly suggestive for peripheral pseudodrusen in association with at least 3 other TIMP3 mutations. 24,25,28,32,34,45 This indicates that peripheral pseudodrusen are another characteristic and relatively frequent lesion occurring in patients with SFD, at least at a certain stage of the disease. We are not aware of reports on other monogenic model diseases associated with peripheral pseudodrusen, and there may be different or additional pathophysiologic factors than those predisposing to the development of RPD.…”

Section: Discussionmentioning

confidence: 94%

“…23e25,31e34 Descriptive terms included exudates, 25 colloid bodies, 32 small white spots, 33 small yellowish subretinal deposits, 31 or drusen-like deposits. 34 The recent improvement of reliable RPD detection and their differentiation from other lesions, such as drusen, with high-resolution multimodal imaging technologies may explain why the association of RPD with SFD has been unravelled only now. Histologic confirmation currently is lacking, and previous studies on SFD mostly were performed in donor eyes with advanced pathologic features, making the detection of subretinal deposits challenging.…”

Section: Discussionmentioning

confidence: 98%

Reticular Pseudodrusen in Sorsby Fundus Dystrophy

et al. 2015

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“…However, CNV infrequently occurs in patients affected by hereditary retinal dystrophies [21]. To date, there are only four reports of BCD associated with the phenotype of CNV [14], [22], [23], [24],whereas none of them identified causative mutations in CYP4V2 or other genes associated with CNV, such as tissue inhibitor of metalloproteinase 3 ( TIMP3 ) [14], [25]. In addition, the phenotype of BCD associated with a macular hole was only briefly described in two studies without genetic analysis [26], [27].…”

Section: Introductionmentioning

confidence: 99%

Molecular Analysis and Phenotypic Study in 14 Chinese Families with Bietti Crystalline Dystrophy

et al. 2014

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PurposeTo investigate the clinical features and cytochrome P450 family 4 subfamily V polypeptide 2 (CYP4V2) gene mutations in 14 Chinese families with Bietti crystalline dystrophy (BCD).MethodsSeventeen patients from 14 unrelated Chinese families with BCD were recruited for complete clinical ophthalmic examination and genetic study. The 11 exons of CYP4V2 were amplified from genomic DNA of all patients and their family members by polymerase chain reaction (PCR) and then sequenced. Exons of TIMP3 were also sequenced in BCD patient associated with choroidal neovascularization (CNV). One hundred and seventy unrelated healthy Chinese subjects were screened for mutations in CYP4V2.ResultsAll 17 patients with BCD had mutations in CYP4V2; one of these mutations was novel (c.219T>A, p.F73L) and four other mutations had been reported. The p.F73L mutation was a commonly detected mutation in our study (seven out of 34 alleles), either in the homozygous state or in the heterozygous state. Among the patients, considerable phenotypic variability was detected, both within and between families. Screening of TIMP3 did not find any mutation in the BCD patient associated with CNV.ConclusionThe novel CYP4V2 c.219T>A (p.F73L) mutation may be another recurrent mutation in Chinese patients with BCD. Our study expands the mutation spectrum of CYP4V2 and characterizes novel genotype–phenotype associations in Chinese patients with BCD.

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A Novel Mutation at the N-Terminal Domain of the Timp3 Gene in Sorsby Fundus Dystrophy

Cited by 19 publications

References 24 publications

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

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

Reticular Pseudodrusen in Sorsby Fundus Dystrophy

Molecular Analysis and Phenotypic Study in 14 Chinese Families with Bietti Crystalline Dystrophy

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