Two familial microduplications of 15q26.3 causing overgrowth and variable intellectual disability with normal copy number of IGF1R

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• 作者：Melanie Leffler^a ; ¹ ; Sanna Puusepp^b ; ¹ ; Olga Žilina^b ; ^c ; Ying Zhu^a ; Kati Kuuse^b ; Nicole Bain^d ; Trent Burgess^e ; ^f ; Katrin &Otilde ; unap^b ; ^g ; Michael Field^a ; ^{Mike.field@health.nsw.gov.au" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Chromosome 15q26.3 ; Microduplication syndrome ; Postnatal overgrowth ; Intellectual disability
• 刊名：European Journal of Medical Genetics
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：59
• 期：4
• 页码：257-262
• 全文大小：1159 K

文摘

Terminal duplications of 15q26.3 are associated with an overgrowth phenotype, distinct facial features and intellectual disability, with the smallest reported microduplication to date being 3.16 Mb in size. We report two familial 15q26.3 microduplication cases that are less than half this size, re-defining the minimal critical region for this duplication syndrome. In both families the duplication (albeit a complex copy number gain in one family) is associated with tall stature, early speech delay and variable cognitive problems. Neither familial copy number gains encompass the gene encoding for the insulin-like growth factor 1 receptor (IGF1R), the most-cited candidate for the overgrowth phenotype. In one family, whole genome sequence data and break point mapping excludes disruption of known IGF1R regulatory elements due to potential insertion within these elements. These cases highlight the possibility that the distal region of 15q contains another gene regulating human growth, with LRRK1 being a potential candidate.