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Titolo:
PARENTAL SOMATIC AND GERM-LINE MOSAICISM FOR A FBN2 MUTATION AND ANALYSIS OF FBN2 TRANSCRIPT LEVELS IN DERMAL FIBROBLASTS
Autore:
PUTNAM EA; PARK ES; AALFS CM; HENNEKAM RCM; MILEWICZ DM;
Indirizzi:
UNIV TEXAS,SCH MED,DEPT INTERNAL MED,6431 FANNIN,MSB 1614 HOUSTON TX 77030 UNIV TEXAS,SCH MED,DEPT INTERNAL MED HOUSTON TX 77030 ST LUKES HOSP,TEXAS HEART INST,DIV CARDIOVASC RES HOUSTON TX 00000 UNIV AMSTERDAM,ACAD MED CTR,DEPT PEDIAT,FAC MED NL-1105 AZ AMSTERDAM NETHERLANDS
Titolo Testata:
American journal of human genetics
fascicolo: 4, volume: 60, anno: 1997,
pagine: 818 - 827
SICI:
0002-9297(1997)60:4<818:PSAGMF>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEONATAL MARFAN-SYNDROME; FIBRILLIN GENES; MISSENSE MUTATION; MESSENGER-RNA; SEQUENCE; IDENTIFICATION; POLYMORPHISMS; ERYTHROCYTES; EXPRESSION; DIAGNOSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
38
Recensione:
Indirizzi per estratti:
Citazione:
E.A. Putnam et al., "PARENTAL SOMATIC AND GERM-LINE MOSAICISM FOR A FBN2 MUTATION AND ANALYSIS OF FBN2 TRANSCRIPT LEVELS IN DERMAL FIBROBLASTS", American journal of human genetics, 60(4), 1997, pp. 818-827

Abstract

Congenital contractural arachnodactyly (CCA) is an autosomal dominantdisorder that is phenotypically related to the Marfan syndrome. CCA has recently been shown to result from mutations in the FBN2 gene, which encodes an elastin-associated microfibrillar protein called fibrillin-2. Two siblings are reported here with classic manifestations of CCAwith unaffected parents. Analysis of the FBN2 cDNA from dermal fibroblasts from one of the affected siblings revealed a heterozygous exon splicing error deleting nt 3722-3844 of the FBN2 mRNA. This cDNA deletion resulted in selective removal of one of the 43 calcium-binding EGF-like domains of the fibrillin-2 protein. Analysis of the FBN2 gene in the affected siblings' DNA indicated that the splicing error resulted from an A-to-G transition 15 nt upstream from the 3' splice site of the intron. The genomic mutation resulting in the splicing error alters a putative branch point sequence important for lariat formation, an intermediate structure of normal splicing. The mutation was detectable in DNA from the father's hair bulbs and buccal cells but not his white blood cell DNA, indicating that the father was a somatic mosaic. Analysis of transcript levels by use of dermal fibroblasts from the probanddemonstrated that the FBN2 allele containing the exon deletion was expressed at a higher level than the allele inherited from the mother. These results indicate that FBN2 exon splicing errors are a cause of CCA, furthering the understanding of the molecular basis of this disorder. In addition, the demonstration of gonadal mosaicism in the FBN2 gene is important for accurate genetic counseling of families with sporadic cases of CCA. Finally, the preferential expression of the mutated FBN2 allele in dermal fibroblasts may have implications for understanding the pathogenesis and rarity of CCA.

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Documento generato il 24/09/20 alle ore 18:58:39