High creatine kinase levels and white matter changes: clinical and genetic spectrum of congenital muscular dystrophies with laminin alpha-2 deficiency.
Primary deficiency of laminin alpha-2 due to mutations in the LAMA2 gene accounts for 30% of all patients with congenital muscular dystrophy. Here, we present seven patients with partial or total laminin alpha-2 deficiency (MDC1A) with a wide clinical spectrum, ranging from ambulant patients to patients who were never able to stand or sit. We identified two pathogenic mutations in the LAMA2 gene in all patients except for one patient in whom only one mutation was found. Six of the mutations were previously undescribed. In some of the milder cases, laminin alpha-2 expression in the muscle biopsy was only slightly reduced. These findings emphasize that analysis of the LAMA2 gene might be necessary in patients with muscle weakness, cerebral white matter changes and high creatine kinase levels, even in the presence of laminin alpha-2 in the muscle biopsy.
Division of Neuropediatrics and Muscle Disorders, University Medical Centre, Freiburg, Germany; Division Pediatria, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile.
Maria de los Angeles
Mde L
Beytía
Department of Human Genetics, Ruhr-University Bochum, Germany.
Gabriele
G
Dekomien
Department of Human Genetics, Ruhr-University Bochum, Germany.
Sabine
S
Hoffjan
Division of Neuropediatrics and Muscle Disorders, University Medical Centre, Freiburg, Germany.
Verena
V
Haug
Division of Neuropediatrics and Muscle Disorders, University Medical Centre, Freiburg, Germany.
Constantin
C
Anastasopoulos
Division of Neuropediatrics and Muscle Disorders, University Medical Centre, Freiburg, Germany. Electronic address: janbernd.kirschner@uniklinik-freiburg.de.
Janbernd
J
Kirschner
D000293:Adolescent; D000328:Adult; D002648:Child; D003402:Creatine Kinase / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D007797:Laminin / Q000172:deficiency / Q000235:genetics*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000151:congenital* / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D066127:White Matter / Q000473:pathology; D055815:Young Adult
D007797:Laminin; C102645:laminin alpha 2; D003402:Creatine Kinase
Congenital muscular dystrophy; Genetics; LAMA2; Laminin alpha-2 deficiency; Merosin; White matter abnormality