✦ LIBER ✦

Glycogen storage disease type II: Genetic and biochemical analysis of novel mutations in infantile patients from Turkish ancestry

✍ Scribed by Monique M. P. Hermans; Marian A. Kroos; Jan A. M. Smeitink; Ans T. van der Ploeg; Wim J. Kleijer; Arnold J. J. Reuser

Publisher: John Wiley and Sons
Year: 1998
Tongue: English
Weight: 192 KB
Volume: 11
Category: Article
ISSN: 1059-7794
DOI: 10.1002/(sici)1098-1004(1998)11:3<209::aid-humu5>3.0.co;2-c

No coin nor oath required. For personal study only.

✦ Synopsis

Glycogen Storage Disease type II (GSDII) is caused by the deficiency of lysosomal a-glucosidase (acid maltase). This paper reports on the characterization of the molecular defects in 6 infantile patients from Turkish ancestry. Five of the 6 patients had reduced levels of the lysosomal a-glucosidase precursor. Conversion to mature enzyme was impaired in all cases, and the lysosomal a-glucosidase activity in all patients fibroblasts was less than 0.5% of control. DNA sequence analysis revealed 3 new mutations. One mutation, found in 3 patients in homozygous form, was a double insertion in exon 19 (2471AG®CAGG) leading to a frameshift after Pro 913. It is the first insertion mutation described in the lysosomal a-glucosidase gene. Two patients were homozygous for missense mutations leading to the substitution of Ser to Pro at amino acid 566 (S566P) in one case and of Pro to Arg at amino acid 768 (P768R) in the other. One patient was found to have a Gly to Arg missense mutation at amino acid 643 (G643R), previously identified in an adult patient (Hermans et al., 1993), combined with a silent second allele. The latter 3 mutations were introduced in the wild type lysosomal a-glucosidase cDNA and expressed in COS cells to analyze their effect. Precursor species of 110 kD were formed but the maturation was impaired. As a result there was an overall deficiency of catalytic activity, which is in accordance with the findings in the patients fibroblasts and with the clinical phenotype.

📜 SIMILAR VOLUMES

Novel mutations in African American pati

Novel mutations in African American patients with glycogen storage disease type II

✍ Nina Raben; Eunice Lee; Laura Lee; Rochelle Hirschhorn; Paul H. Plotz 📂 Article 📅 1999 🏛 John Wiley and Sons 🌐 English ⚖ 74 KB

The infantile form of GSD II (an inherited deficiency of the lysosomal enzyme, acid α αglucosidase, Pompe disease) is a severe and invariably fatal disease characterized by a rapidly progressive generalized hypotonia, hepatomegaly, and cardiomegaly. We have recently demonstrated that African America

Molecular genetic analysis of 40 patient

Molecular genetic analysis of 40 patients with glycogen storage disease type Ia: 100% mutation detection rate and 5 novel mutations

✍ Hans H. Seydewitz; Dietrich Matern 📂 Article 📅 2000 🏛 John Wiley and Sons 🌐 English ⚖ 23 KB 👁 1 views

Molecular genetic analysis of 40 patients with glycogen storage disease type Ia (GSD Ia) revealed mutations on all 80 alleles and verified the diagnosis in all patients. At least 7 patients were diagnosed with GSD Ia solely on the basis of clinical findings prior to our analysis. Five mutations, Q20

Identification of four novel mutations i

Identification of four novel mutations in the alpha glucosidase gene in five Italian patients with infantile onset glycogen storage disease type II

✍ Pittis, Maria Gabriela ;Montalvo, Anna Lisa E. ;Miocic, Snjezana ;Martini, Crist 📂 Article 📅 2003 🏛 John Wiley and Sons 🌐 English ⚖ 107 KB 👁 1 views

The identification of five novel mutatio

The identification of five novel mutations in the lysosomal acid a-(1,4) glucosidase gene from patients with glycogen storage disease type II

✍ Clare E. Beesley; Anne H. Child; Magdi H. Yacoub 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 English ⚖ 165 KB 👁 2 views

The autosomal recessive disorder Glycogen Storage Disease Type II (GSDII) is caused by a deficiency in the lysosomal enzyme acid -glucosidase. We have optimised a procedure to use fluorescent DNA sequencing technology to screen for mutations within the -glucosidase gene from UK patients with GSDII.

Glycogen storage disease type Ia: Molecu

Glycogen storage disease type Ia: Molecular diagnosis of 51 Japanese patients and characterization of splicing mutations by analysis of ectopically transcribed mRNA from lymphoblastoid cells

✍ Akanuma, Jun; Nishigaki, Toshinori; Fujii, Kunihiro; Matsubara, Yoichi; Inui, Ko 📂 Article 📅 2000 🏛 John Wiley and Sons 🌐 English ⚖ 48 KB 👁 2 views

Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive disorder of glycogen metabolism caused by a deficiency of glucose-6-phosphatase (G6Pase) that is expressed in the liver, kidney, and intestinal mucosa. Clinical manifestations include short stature, hepatomegaly, hypoglycemia, hyper

Identification of three novel mutations

Identification of three novel mutations (Q54P, W70X and T108I) in the glucose-6-phosphatase gene of patients with glycogen storage disease type Ia

✍ Pascale Trioche; Jeanne Francoual; Jacqueline Chalas; Liliane Capel; Olivier Ber 📂 Article 📅 1999 🏛 John Wiley and Sons 🌐 English ⚖ 10 KB 👁 1 views

Three novel mutations, Q54P, W70X and T108I, were identified in the gene encoding glucose-6phosphatase in three patients with glycogen storage disease type Ia. Two sibs of Portuguese origin were homozygous for the Q54P mutation whereas the third patient, originating from both France and Lebanon, was