title: A novel mutation (C1425Y) in the FBN2 gene in a father and son with congenital contractural arachnodactyly.
abstract: Congenital contractural arachnodactyly (Beals syndrome) is a rare autosomal dominantly inherited connective tissue disorder characterized by flexion contractures, arachnodactyly, crumpled ears, and mild muscular hypoplasia. Here, a father and son with congenital contractural arachnodactyly features were identified. After sequencing 15 exons (22 to 36) of the FBN2 gene, a novel mutation (C1425Y) was found in exon 33. This de novo mutation presented first in the father and was transmitted to his son, but not in the other 14 unaffected family members and 365 normal people. The C1425Y mutation occurs at the 19th cbEGF domain. Cysteines in this cbEGF domain are rather conserved in species, from human down to ascidian. The cbEGF12-13 in human FBN1 was employed as the template to perform homology modeling of cbEGF18-19 of human FBN2 protein. The mutation has also been evaluated by further prediction tools, for example, SIFT, Blosum62, biochemical Yu's matrice, and UMD-Predictor tool. In all analysis, the mutation is predicted to be pathogenic. Thus, the structure destabilization by C1425Y might be the cause of the disorder.
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Lei
authors.forename: Hong-Xiang
authors.initials: HX
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Cheng
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Hong
authors.initials: H
authors.lastname: Li
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000595:Amino Acid Sequence; D054119:Arachnodactyly / Q000235:genetics*; D002675:Child, Preschool; D016384:Consensus Sequence; D005220:Fathers; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D013081:Sperm Motility / Q000502:physiology; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605723:FBN2 protein, human