Molecular Characterization of a De Novo 6q24.2q25.3 Duplication Interrupting UTRN in a Patient With Arthrogryposis

作者：Tabet Anne Claude^*; Aboura Azzedine; Gerard Marion; Pilorge Marion; Dupont Celine; Gadisseux Jean Francois; Hervy Nadege; Pipiras Eva; Delahaye Andree; Kanafani Samia; Verloes Alain; Benzacken Brigitte; Betancur Catalina

来源：American Journal of Medical Genetics, Part A, 2010, 152A(7): 1781-1788.

DOI：10.1002/ajmg.a.33433

• 6q duplication syndrome
• joint contracture
• utrophin
• array-CGH
• qPCR

Chromosome 6q duplications have been documented repeatedly, allowing the delineation of a "6q duplication syndrome," characterized by hypertelorism, downslanting palpebral fissures, tented upper lip, short neck, severe mental and growth retardation, and joint contractures. Most reported cases result from malsegregation of a reciprocal translocation leading to a terminal 6q duplication and partial monosomy of another chromosome. Only 11 cases of de novo pure duplication have been reported so far. The breakpoints do not appear to be recurrent, but in most cases they have not been characterized molecularly, precluding genotype phenotype correlation. We report on an 8-year-old girl with a phenotype consistent with mild 6q duplication syndrome, including characteristic physical findings, mild mental retardation, and joint contractures. She carries a 13 Mb de novo 6q24.2q25.3 duplication, diagnosed by high-resolution karyotype and confirmed by array-CGH. Molecular characterization of the duplicated segment with quantitative PCR showed that the proximal breakpoint is localized within the UTRN gene, encoding utrophin, the autosomal homologue of dystrophin. We discuss the possible implication of UTRN in arthrogryposis associated with duplications spanning the 6q23q26 region.

• 出版日期2010-7