Homozygosity for the common GAA gene splice site mutation c.-32-13T>G in Pompe disease is associated with the classical adult phenotypical spectrum
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Homozygosity for the common GAA gene splice site mutation c.-32-13T>G in Pompe disease is associated with the classical adult phenotypical spectrum. / Musumeci, Olimpia; Thieme, Andrea; Claeys, Kristl G; Wenninger, Stephan; Kley, Rudolf A; Kuhn, Marius; Lukacs, Zoltan; Deschauer, Marcus; Gaeta, Michele; Toscano, Antonio; Gläser, Dieter; Schoser, Benedikt.
In: NEUROMUSCULAR DISORD, Vol. 25, No. 9, 09.2015, p. 719-24.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Homozygosity for the common GAA gene splice site mutation c.-32-13T>G in Pompe disease is associated with the classical adult phenotypical spectrum
AU - Musumeci, Olimpia
AU - Thieme, Andrea
AU - Claeys, Kristl G
AU - Wenninger, Stephan
AU - Kley, Rudolf A
AU - Kuhn, Marius
AU - Lukacs, Zoltan
AU - Deschauer, Marcus
AU - Gaeta, Michele
AU - Toscano, Antonio
AU - Gläser, Dieter
AU - Schoser, Benedikt
N1 - Copyright © 2015 Elsevier B.V. All rights reserved.
PY - 2015/9
Y1 - 2015/9
N2 - Homozygosity for the common Caucasian splice site mutation c.-32-13T>G in intron 1 of the GAA gene is rather rare in Pompe patients. We report on the clinical, biochemical, morphological, muscle imaging, and genetic findings of six adult Pompe patients from five unrelated families with the c.-32-13T>G GAA gene mutation in homozygous state. All patients had decreased GAA activity and elevated creatine kinase levels. Five patients, aged between 43 and 61 years (median 53 years), initially presented with myalgia, hyperCKaemia, and/or exercise induced fatigue at an age of onset (12-55 years). All but one had proximal lower limb weakness combined with axial weakness and moderate respiratory insufficiency; the sixth patient presented with hyperCKaemia only. Muscle biopsies showed PAS-positive vacuolar myopathy with lysosomal changes and reduced GAA activity. Muscle MRI of lower limb muscles revealed a moderate adipose substitution of the gluteal muscles, biceps femoris and slight fatty infiltration of all thigh muscles. One MRI of the respiratory muscles revealed a diaphragmatic atrophy with unilateral diaphragm elevation. So, the common Caucasian, so called mild, splice site mutation c.-32-13T>G in intron 1 of the GAA gene in a homozygote status reflects the full adult Pompe disease phenotype severity spectrum.
AB - Homozygosity for the common Caucasian splice site mutation c.-32-13T>G in intron 1 of the GAA gene is rather rare in Pompe patients. We report on the clinical, biochemical, morphological, muscle imaging, and genetic findings of six adult Pompe patients from five unrelated families with the c.-32-13T>G GAA gene mutation in homozygous state. All patients had decreased GAA activity and elevated creatine kinase levels. Five patients, aged between 43 and 61 years (median 53 years), initially presented with myalgia, hyperCKaemia, and/or exercise induced fatigue at an age of onset (12-55 years). All but one had proximal lower limb weakness combined with axial weakness and moderate respiratory insufficiency; the sixth patient presented with hyperCKaemia only. Muscle biopsies showed PAS-positive vacuolar myopathy with lysosomal changes and reduced GAA activity. Muscle MRI of lower limb muscles revealed a moderate adipose substitution of the gluteal muscles, biceps femoris and slight fatty infiltration of all thigh muscles. One MRI of the respiratory muscles revealed a diaphragmatic atrophy with unilateral diaphragm elevation. So, the common Caucasian, so called mild, splice site mutation c.-32-13T>G in intron 1 of the GAA gene in a homozygote status reflects the full adult Pompe disease phenotype severity spectrum.
KW - Adult
KW - Disease Progression
KW - Female
KW - Glycogen Storage Disease Type II
KW - Homozygote
KW - Humans
KW - Male
KW - Middle Aged
KW - Muscle, Skeletal
KW - Mutation
KW - Phenotype
KW - RNA Splice Sites
KW - alpha-Glucosidases
KW - Case Reports
KW - Journal Article
U2 - 10.1016/j.nmd.2015.07.002
DO - 10.1016/j.nmd.2015.07.002
M3 - SCORING: Journal article
C2 - 26231297
VL - 25
SP - 719
EP - 724
JO - NEUROMUSCULAR DISORD
JF - NEUROMUSCULAR DISORD
SN - 0960-8966
IS - 9
ER -