GM21941

GM21941 Fibroblast from Skin, Unspecified

Description:

MARFAN SYNDROME; MFS
FIBRILLIN 1; FBN1

Affected:

Yes

Sex:

Female

Age:

No Data

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Biopsy Source

Unspecified

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Unspecified

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; classic features; donor subject has a C>T transition (silent mutation) at nucleotide 6354 in exon 51 of the FBN1 gene (6354C>T) resulting in the in-frame skipping of exon 51 (del 66 bp)

Characterizations

PDL at Freeze

7.35

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin confirmed by LINE assay

Gene

FBN1

Chromosomal Location

15q21.1

Allelic Variant 1

134797.0030; MARFAN SYNDROME, CLASSIC

Identified Mutation

6354C>T,EX51DEL,ILE2118ILE; Liu et al. (1997) carried out a systematic mutation search of PCR-amplified transcripts of the FBN1 gene from patients with Marfan syndrome. By long RT-PCR and restriction enzyme digestions, they identified skipping of FBN1 exons in 10% of Marfan cases. All but 1 of the these were due to sequence alterations at splice sites. In skin fibroblasts derived from a patient with classic Marfan syndrome, an abnormally migrating restriction fragment was identified and found to represent deletion of 66 bp due to in-frame skipping of the entire exon 51. This exon encodes the 3-prime portion of 1 of the 7 8-cysteine domains in FBN1 that is similar to a motif found in transforming growth factor-beta-1 binding protein (150390). Sequencing of exon 51 and surrounding splice sites, amplified from genomic DNA with intron primers, identified only 1 sequence variation unique to this sample: a C-to-T transition (6354C-T) at position +41 of exon 51. This mutation changes codon 2118 from AUC to AUU, both of which encode isoleucine. Liu et al. (1997) stated that this nucleotide change is unlikely to affect known binding sites of the splicing machinery. Further studies indicated that the skipping of exon 51 in these cells was due solely to the silent mutation, 6354C-T. Skipping of exon 51 associated with a 6339T-G mutation that changes a tyrosine (TAT) to a termination (TAG) codon (134797.0008) was previously reported as the cause of exon 51 skipping (Dietz et al., 1993; Dietz and Kendzior, 1994). Liu et al. (1997) commented that skipping caused by a silent mutation suggests the existence of an alternative mechanism of exon skipping yet to be discovered.