title: Molecular characterization of an X(p21.2;q28) chromosomal inversion in a Duchenne muscular dystrophy patient with mental retardation reveals a novel long non-coding gene on Xq28.
abstract: Duchenne muscular dystrophy (DMD) is the most common inherited muscular disease and is characterized by progressive muscle wasting. DMD is caused by mutations in the dystrophin gene on Xp21.2. One-third of DMD cases are complicated by mental retardation, but the pathogenesis of this is unknown. We have identified an intrachromosomal inversion, inv(X)(p21.2;q28) in a DMD patient with mental retardation. We hypothesized that a gene responsible for the mental retardation in this patient would be disrupted by the inversion. We localized the inversion break point by analysis of dystrophin complementary DNA (cDNA) and fluorescence in situ hybridization. We used 5' and 3' rapid amplification of cDNA ends to extend the known transcripts, and reverse transcription-PCR to analyze tissue-specific expression. The patient's dystrophin cDNA was separated into two fragments between exons 18 and 19. Exon 19 was dislocated to the long arm of the X-chromosome. We identified a novel 109-bp sequence transcribed upstream of exon 19, and a 576-bp sequence including a poly(A) tract transcribed downstream of exon 18. Combining the two novel sequences, we identified a novel gene, named KUCG1, which comprises three exons spanning 50 kb on Xq28. The 685-bp transcript has no open-reading frame, classifying it as a long non-coding RNA. KUCG1 mRNA was identified in brain. We cloned a novel long non-coding gene from a chromosomal break point. It was supposed that this gene may have a role in causing mental retardation in the index case.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Thi Hoai Thu
authors.initials: TH
authors.lastname: Tran
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Mariko
authors.initials: M
authors.lastname: Yagi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Lee
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Awano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okinaga
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
mesh_terms: D001921:Brain / Q000378:metabolism; D002675:Child, Preschool; D019457:Chromosome Breakage; D007446:Chromosome Inversion; D041321:Chromosomes, Human, X / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D016189:Dystrophin / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000150:complications / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018076:DNA, Complementary; D016189:Dystrophin; D062085:RNA, Long Noncoding; D012333:RNA, Messenger