Intellectual ability in the duchenne muscular dystrophy and dystrophin gene mutation location.
Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy during childhood. Mutations in dystrophin (DMD) gene are also recognized as a cause of cognitive impairment. We aimed to determine the association between intelligence level and mutation location in DMD genes in Serbian patients with DMD. Forty-one male patients with DMD, aged 3 to 16 years, were recruited at the Clinic for Neurology and Psychiatry for Children and Youth in Belgrade, Serbia. All patients had defined DMD gene deletions or duplications [multiplex ligation-dependent probe amplification (MLPA), polymerase chain reaction (PCR)] and cognitive status assessment (Wechsler Intelligence Scale for Children, Brunet-Lezine scale, Vineland-Doll scale). In 37 patients with an estimated full scale intelligence quotient (FSIQ), six (16.22%) had borderline intelligence (70<FSIQ ≤85), while seven (18.92%) were intellectually impaired (FSIQ <70). The FSIQ was not associated with proximal and distal mutations when boundaries were set at exons 30 and 45. However, FSIQ was statistically significantly associated with mutation location when we assumed their functional consequence on dystrophin isoforms and when mutations in the 5'-untranslated region (5'UTR) of Dp140 (exons 45-50) were assigned to affect only Dp427 and Dp260. Mutations affecting Dp140 and Dp71/Dp40 have been associated with more frequent and more severe cognitive impairment. Finally, the same classification of mutations explained the greater proportion of FSIQ variability associated with cumulative loss of dystrophin isoforms. In conclusion, cumulative loss of dystrophin isoforms increases the risk of intellectual impairment in DMD and characterizing the genotype can define necessity of early cognitive interventions in DMD patients.
Clinic for Neurology and Psychiatry for Children and Youth, Belgrade, Serbia ; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
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Milic Rasic
Clinic for Neurology and Psychiatry for Children and Youth, Belgrade, Serbia.
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D
Vojinovic
Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
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J
Pesovic
Clinic for Neurology and Psychiatry for Children and Youth, Belgrade, Serbia.
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Mijalkovic
Clinic for Neurology and Psychiatry for Children and Youth, Belgrade, Serbia.
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Lukic
Clinic for Neurology and Psychiatry for Children and Youth, Belgrade, Serbia.
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J
Mladenovic
Clinic for Neurology and Psychiatry for Children and Youth, Belgrade, Serbia.
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A
Kosac
Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
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I
Novakovic
Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
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Maksimovic
Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
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Romac
Clinic for Neurology and Psychiatry for Children and Youth, Belgrade, Serbia.
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S
Todorovic
Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
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D
Savic Pavicevic
Duchenne muscular dystrophy (DMD); dystrophin isoform; intellectual impairment