Universität zu Köln

Khan, Arif O., Bolz, Hanno J. and Bergmann, Carsten (2014). Results of fibrillin-1 gene analysis in children from inbred families with lens subluxation. J. AAPOS, 18 (2). S. 134 - 140. NEW YORK: MOSBY-ELSEVIER. ISSN 1528-3933

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Abstract

BACKGROUND Autosomal dominant mutation of the FBNI gene (fibrillin-1) results in a spectrum of disease (type 1 fibrillopathies) ranging from Marfan syndrome with lens subluxation and cardiovascular complications to milder connective tissues phenotypes. The likelihood of FBNI mutation in children referred to ophthalmologists because of lens subluxation is unclear. We report the results of routine FBN1 sequencing for children from inbred families referred with nontraumatic lens subluxation without cataract or vitreoretinal degeneration. METHODS Medical records of such patients from 2009 to 2012 were retrospectively reviewed. RESULTS Eight identified probands (3-11 years old; 4 boys) from consanguineous and/or endogamous Saudi Arabian families all harbored FBN1 mutation-7 autosomal dominant and 1 autosomal recessive (homozygous). Four mutations were novel. One child had a family history for lens subluxation. Seven had facial and/or skeletal features suggestive of type 1 fibrillinopathy. The parents of the autosomal recessive case were confirmed to be heterozygous carriers without lens subluxation or other clinical signs of type 1 fibrillinopathy. CONCLUSIONS Autosomal dominant type 1 fibrillinopathy was the major cause for lens subluxation in this cohort despite the fact that families were inbred and thus at higher risk for recessive disease. This highlights the frequency of new mutations in the gene and has important implications for genetic counseling and systemic assessment. The autosomal recessive case represents the fourth such case reported to date. Her heterozygous parents were unaffected carriers, suggesting that some FBN1 mutations can act as hypomorphic alleles rather than exhibiting the dominant negative effect typically attributed to FBN1 mutations.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Khan, Arif O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bolz, Hanno J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergmann, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-441436
DOI:	10.1016/j.jaapos.2013.11.012
Journal or Publication Title:	J. AAPOS
Volume:	18
Number:	2
Page Range:	S. 134 - 140
Date:	2014
Publisher:	MOSBY-ELSEVIER
Place of Publication:	NEW YORK
ISSN:	1528-3933
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ISOLATED ECTOPIA LENTIS; PATHOGENIC FBN1 MUTATIONS; WEILL-MARCHESANI-SYNDROME; MARFAN-SYNDROME; MISSENSE MUTATIONS; TYPE-1 FIBRILLINOPATHIES; DIAGNOSTIC-CRITERIA; LTBP2 MUTATIONS; PHENOTYPE; ADAMTSL4 Multiple languages Ophthalmology; Pediatrics Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44143