Complete skipping of exon 66 due to novel mutations of the dystrophin genewas identified in two Japanese families of Duchenne muscular dystrophy with severe mental retardation

Severe mental retardation is a rare complication of Duchenne muscular dystr ophy (DMD). Here we report that two DMD cases showing severe mental retarda tion exhibit the same exon skipping event induced by different intron mutat ions. In the two Japanese DMD patients studied, the complete sequence of ex on 66 of the dystrophin gene was found to be absent from the dystrophin mRN A, creating a premature stop codon in exon 67. Novel point mutations at the consensus sequence of the splice donor site of intron 66 (T9857(+2) to C i n one case and G9857(+5) to T in the other case) were found to be the cause of complete exon skipping. Remarkably, severe mental retardation cosegrega ted with an tron 66-skipping event in their families. Furthermore, pachygyr ia was disclosed by magnetic resonance imaging (MRI) examination of the bra in of one ease. Our results suggested that exon 66 skipping should be exami ned in DMD cases with a severe form of mental retardation, (C) 2000 Elsevie r Science B.V. All rights reserved.