A homozygous missense mutation (A659D) in the myophosphorylase gene in a Spanish patient with McArdle's disease

Martín, Miguel; Rubio, Juan Carlos Colomer; Campos, Yolanda; Ricoy, José Ramón; Cabello, Ana; Arenas, Joaquı́n

doi:10.1016/s0960-8966(99)00124-8

Cited by 8 publications

(3 citation statements)

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“…Of them, 10 have been reported elsewhere: 5′ivs14 g→a,12 753 delA,14, 15 L115P,19 N684Y,16 794/795 delAA,22 R193W,22 T487N,21 A659D,23 W797R,20, 30 and 387 insA/del 8 bp 24. Patients with L115P, N684Y, 794/795 delAA, R193W, T487N, A659D, and 387 insA/del 8 bp mutations are identical to those in whom these mutations have been first reported 16, 19, 21–24. Of the 9 patients with the W797R mutation described here, 4 have been documented in previous reports 20, 30…”

Section: Resultsmentioning

confidence: 99%

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Molecular heterogeneity of myophosphorylase deficiency (Mcardle's disease): A genotype‐phenotype correlation study

Martín

Rubio

Buchbinder

et al. 2001

Annals of Neurology

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We report on 54 Spanish patients with McArdle's disease from 40 unrelated families. Molecular analysis revealed that the most common R49X mutation was present in 70% of patients and 55% of alleles. The G204S mutation was less frequent and found in 14.8% of patients and 9% of mutant alleles. The W797R mutation was observed in 16.5% of patients, accounting for 13.7% of mutant alleles. Moreover, 78% of mutant alleles among Spanish patients can be identified by using polymerase chain reaction-restriction fragment length polymorphism analysis for the R49X, G204S, and W797R mutations, which makes noninvasive diagnosis possible through molecular genetic analysis of blood DNA. Six novel mutations were found. Three were missense mutations, E348K, R601W, and A703V; two nonsense mutations, E124X and Q754X; and one single base pair deletion, 533 delA. No clear genotype-phenotype correlation emerges from our study. Most of the mutations of uncharged and solvent inaccessible residues and the truncations must disrupt the basic structure of the protein. The mutations of charged residues would be expected to interfere with internal hydrogen bonding networks, introducing severe incompatible partnering that is caused by poor packing or electrostatic repulsions.

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Section: Resultsmentioning

confidence: 99%

“…Molecular heterogeneity has been demonstrated by the identification of various different mutations in the coding regions or splice sites of the gene 9–24. The most common among European and US patients is a nonsense mutation at codon 49 in exon 1 (R49X) 9, 11, 15, 25–28…”

mentioning

confidence: 99%

Molecular heterogeneity of myophosphorylase deficiency (Mcardle's disease): A genotype‐phenotype correlation study

Martín

Rubio

Buchbinder

et al. 2001

Annals of Neurology

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“…Although the R49X mutation is clearly the most prevalent in white patients, patients with McArdle's disease manifest considerable allelic heterogeneity, a characteristic shared with other glycogenoses, such as acid maltase and phosphofructokinase deficiencies 11, 14. The work done on Spanish patients has made a significant contribution to showing this heterogeneity, as almost 40% of the mutations in the gene have been identified in patients from this population 1, 4, 5, 8–11, 16…”

Section: Discussionmentioning

confidence: 98%

Two novel mutations in the muscle glycogen phosphorylase gene in McArdle's disease

Gámez¹,

Rubio

Martín

et al. 2003

Muscle and Nerve

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We report on a Spanish family with myophosphorylase (EC 2.4.1.1) deficiency (McArdle's disease). The proband and his symptomatic sister were compound heterozygous for two novel mutations: a T-to-G transversion in exon 14 (c1722 T>G) that changes a tyrosine to a stop codon (Y573X), and a G-to-A transition in exon 15 (c1827 G>A) that disrupts the consensus signal at the donor splicing site. These findings further expand knowledge of the genetic bases of muscle glycogen phosphorylase deficiency.

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A New Rare Mutation (691delCC/insAAA) in Exon 17 of the PYGM Gene Causing McArdle Disease

Quintáns

Sánchez-Andrade²,

Teijeira³

et al. 2004

Arch Neurol

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To investigate the genetic effect of a new mutation found in exon 17 of the myophosphorylase (PYGM) gene as a cause of McArdle disease (also known as type 5 glycogenosis). Patients: A Spanish patient with McArdle disease was screened for 3 common mutations in the PYGM gene (R49X, W797R, and G204S), as previously described. The patient was heterozygous for R49X. To find other mutations, the coding sequence of the entire PYGM gene was sequenced. The carrier status of his relatives was also studied. Results: A novel rare mutation was found in codon 691 of exon 17. This is an insertion/deletion (indel) and consists simultaneously of a deletion of 2 bases and an insertion of 3 bases (691delCC/insAAA). A restriction analysis was designed to simplify the detection method. Conclusions: The 691delCC/insAAA is the third indel described in the PYGM gene. Indels represent 0.95% of the total reported mutations in the Human Gene Mutation Database. The molecular origin of this mutation is not fully understood. These findings point again to the allelic heterogeneity of McArdle disease.

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A homozygous missense mutation (A659D) in the myophosphorylase gene in a Spanish patient with McArdle's disease

Cited by 8 publications

References 9 publications

Molecular heterogeneity of myophosphorylase deficiency (Mcardle's disease): A genotype‐phenotype correlation study

Molecular heterogeneity of myophosphorylase deficiency (Mcardle's disease): A genotype‐phenotype correlation study

Two novel mutations in the muscle glycogen phosphorylase gene in McArdle's disease

A New Rare Mutation (691delCC/insAAA) in Exon 17 of the PYGM Gene Causing McArdle Disease

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