Identification of a novel AluSx-mediated deletion of exon 3 in the SBDS gene in a patient with Shwachman-Diamond syndrome

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Elisio Costa (Author) FFUP; Frederico Duque (Author) Other; Jorge Oliveira (Author) Other; Paula Garcia (Author) Other; Isabel Goncalves (Author) Other; Luisa Diogo (Author) Other; Rosario Santos (Author) Other

Journal

Title: Blood Cells, Molecules, and Diseases

Vol. 39

Pages: 96-101

ISSN: 1079-9796

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 14 Citations

Scopus - 14 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-004-8Z4

DOI: 10.1016/j.bcmd.2007.02.002

Abstract (EN): Shwachman-Diamond syndrome (SDS) is caused by mutations in the SBDS gene, most of which are the result of gene conversion events involving its highly homologous pseudogene SBDSP. Here we describe the molecular characterization of the first documented gross deletion in the SBDS gene, in a 4-year-old Portuguese girl with SDS. The clinical diagnosis was based on the presence of hematological symptoms (severe anemia and cyclic neutropenia), pancreatic exocrine insufficiency and skeletal abnormalities. Routine molecular screening revealed heterozygosity for the common splicing mutation c.258+2T > C, and a further step-wise approach led to the detection of a large deletion encompassing exon 3, the endpoints of which were subsequently delineated at the gDNA level. This novel mutation (c.258+374 459+250del), predictably giving rise to an internally deleted polypeptide (p.107_Gln 153del), appears to have arisen from an excision event mediated by AluSx elements which are present in introns 2 and 3. Our case illustrates the importance of including gross deletion screening in the SDS diagnostic setting, especially in cases where only one deleterious mutation is detected by routine screening methods. In particular, deletional rearrangements involving exon 3 should be considered, since Alu sequences are known to be an important cause of recurrent mutations.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6