✦ LIBER ✦

Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease

✍ Scribed by Barbara Tappino; Roberta Biancheri; Matthew Mort; Stefano Regis; Fabio Corsolini; Andrea Rossi; Marina Stroppiano; Susanna Lualdi; Agata Fiumara; Bruno Bembi; Maja Di Rocco; David N. Cooper; Mirella Filocamo

Publisher: John Wiley and Sons
Year: 2010
Tongue: English
Weight: 790 KB
Volume: 31
Category: Article
ISSN: 1059-7794
DOI: 10.1002/humu.21367

No coin nor oath required. For personal study only.

✦ Synopsis

The characterization of the underlying GALC gene lesions was performed in 30 unrelated patients affected by Krabbe disease, an autosomal recessive leukodystrophy caused by the deficiency of lysosomal enzyme galactocerebrosidase. The GALC mutational spectrum comprised 33 distinct mutant (including 15 previously unreported) alleles. With the exception of 4 novel missense mutations that replaced evolutionarily highly conserved residues (p.P318R, p.G323R, p.I384T, p.Y490N), most of the newly described lesions altered mRNA processing. These included 7 frameshift mutations (c.61delG, c.408delA, c.521delA, c.1171_1175delCATTCinsA, c.1405_1407delCTCinsT, c.302_308dupAAATAGG, c.1819_1826dupGTTACAGG), 3 nonsense mutations (p.R69X, p.K88X, p.R127X) one of which (p.K88X) mediated the skipping of exon 2, and a splicing mutation (c.1489+1G>A) which induced the partial skipping of exon 13. In addition, 6 previously unreported GALC polymorphisms were identified. The functional significance of the novel GALC missense mutations and polymorphisms was investigated using the MutPred analysis tool. This study, reporting one of the largest genotype-phenotype analyses of the GALC gene so far performed in a European Krabbe disease cohort, revealed that the Italian GALC mutational profile differs significantly from other populations of European origin. This is due in part to a GALC missense substitution (p.G553R) that occurs at high frequency on a common founder haplotype background in patients originating from the Naples region. © 2010 Wiley-Liss, Inc.

📜 SIMILAR VOLUMES

Identification and characterization of n

Identification and characterization of novel collagen VI non-canonical splicing mutations causing ullrich congenital muscular dystrophy

✍ Elena Martoni; Anna Urciuolo; Patrizia Sabatelli; Marina Fabris; Matteo Bovolent 📂 Article 📅 2009 🏛 John Wiley and Sons 🌐 English ⚖ 598 KB

Splicing mutations occurring outside the invariant GT and AG dinucleotides are frequent in disease genes and the definition of their pathogenic potential is often challenging. We have identified four patients affected by Ullrich congenital muscular dystrophy and carrying unusual mutations of COL6 ge

Identification of novel mutations in the

Identification of novel mutations in the MTM1 gene causing severe and mild forms of X-linked myotubular myopathy

✍ Anna Buj-Bello; Valérie Biancalana; Céline Moutou; Jocelyn Laporte; Jean-Louis M 📂 Article 📅 1999 🏛 John Wiley and Sons 🌐 English ⚖ 203 KB 👁 2 views

X-linked myotubular myopathy (XLMTM) is a congenital muscular disease characterized by severe hypotonia and generalized muscle weakness, leading in most cases to early postnatal death. The gene responsible for the disease, MTM1, encodes a dual specificity phosphatase, named myotubularin, which is hi

Identification of three novel mutations

Identification of three novel mutations in the major human skeletal muscle chloride channel gene (CLCN1), causing myotonia congenita

✍ Raffaella Brugnoni; Stefania Galantini; Paolo Confalonieri; Maria Rosa Balestrin 📂 Article 📅 1999 🏛 John Wiley and Sons 🌐 English ⚖ 100 KB 👁 3 views

## Myotonia congenita (MC) is a genetic disease characterized by mutations in the CLCN1 gene (OMIM\*118425) encoding the skeletal muscle voltage-gated chloride channel (ClC-1). Autosomal dominant and recessive forms are observed, characterized by impaired muscle relaxation after forceful contractio

Characterization of 11 novel mutations i

Characterization of 11 novel mutations in the X-linked chronic granulomatous disease (CYBB gene)

✍ Bénédicte Gérard; Jamel El Benna; Françoise Alcain; Marie-Anne Gougerot-Pocidalo 📂 Article 📅 2001 🏛 John Wiley and Sons 🌐 English ⚖ 19 KB

The most frequent form of chronic granulomatous disease (CGD) is caused by inactivation of the CYBB gene, which encodes the gp91-phox subunit of phagocyte NADPH oxidase. This defect prevents phagocytes from producing reactive oxygen species and thus from eradicating bacterial and fungal infections.

Identification and characterization of n

Identification and characterization of novel mutations of the major Fanconi anemia gene FANCA in the Japanese population

✍ Hiroshi Yagasaki; Satoshi Hamanoue; Tsukasa Oda; Tatsutoshi Nakahata; Shigetaka 📂 Article 📅 2004 🏛 John Wiley and Sons 🌐 English ⚖ 324 KB 👁 2 views

Fanconi anemia (FA) is a rare autosomal recessive disorder of hematopoiesis, with at least 11 complementation groups. FANCA, a gene for group A, accounts for the majority of FA patients. Previous studies of FANCA mutations revealed high allelic heterogeneity, frequent occurrence of large deletions,

Identification of novel ATP7B gene mutat

Identification of novel ATP7B gene mutations and their functional roles in Korean patients with Wilson disease

✍ Sangwook Park; Jung-Young Park; Gu-Hwan Kim; Jin-Ho Choi; Kyung-Mo Kim; Jong-Bae 📂 Article 📅 2007 🏛 John Wiley and Sons 🌐 English ⚖ 281 KB 👁 1 views

## Communicated by Jurgen Horst Wilson disease (WND), an autosomal recessive disorder of copper transport, is characterized by excessive accumulation of intracellular copper in liver and extrahepatic tissues because of impaired biliary copper excretion and disturbed incorporation of copper into ce