Tandem duplication of DMD exon 18 associated with epilepsy, macroglossia, and endocrinologic abnormalities.
We describe a patient with Duchenne muscular dystrophy (DMD) who additionally suffered from intractable seizures, severe mental retardation, and a marked macroglossia. He also had endocrinologic abnormalities consisting of growth hormone deficiency, delayed puberty, and adrenal hypoplasia. We detected a duplication of DMD exon 18 and flanking introns that caused a frame-shift and was not removed by corrective splicing. A coincident mutation in the FKRP gene was excluded by direct sequencing. Complex DNA rearrangements, deletions, and duplications >100 kb were excluded through microarray-comparative genomic hybridization (CGH), although we were not able to exclude a second coincident mutation with certainty. In conclusion, we present a case of DMD that conflicts with current understanding of genotype-phenotype relations and discuss putative pathogenetic mechanisms for this uncommon phenotype.
Weiss
Claudia
C
Department of Neuropediatrics, Charité University Medical Center, Augustenburger Platz 1, D-13353 Berlin, Germany. claudia.weiss@charite.de
Jakubiczka
Sibylle
S
Huebner
Angela
A
Klopocki
Eva
E
Kress
Wolfram
W
Voit
Thomas
T
Hübner
Christoph
C
Schuelke
Markus
M
D000309:Adrenal Insufficiency / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000328:Adult; D004252:DNA Mutational Analysis; D016189:Dystrophin / Q000235:genetics*; D004700:Endocrine System Diseases / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D004827:Epilepsy / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D016368:Frameshift Mutation / Q000235:genetics; D020440:Gene Duplication; D005819:Genetic Markers; D005838:Genotype; D013006:Growth Hormone / Q000172:deficiency; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008260:Macroglossia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D010430:Pentosyltransferases; D010641:Phenotype; D010900:Pituitary Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011506:Proteins / Q000235:genetics; D011628:Puberty, Delayed / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D013577:Syndrome; D020080:Tandem Repeat Sequences / Q000235:genetics
D016189:Dystrophin; D005819:Genetic Markers; D011506:Proteins; D013006:Growth Hormone; C443107:FKRP protein, human; D010430:Pentosyltransferases