BACKGROUND: Brachydactyly type A2 (BDA2) is an autosomal dominant disorder. It was recently reported that a 5.9 kb duplication and a 5.5 kb duplication in the region 20p12.2-12.3 are associated with BDA2 in two European families. OBJECTIVE: To characterise a 6-generation Chinese family with 16 members affected by BDA2 and map the gene to 20p12.2-12.3. METHODS AND RESULTS: A 4.6 kb duplication downstream of the bone morphogenetic protein 2 (BMP2) was identified in the family. The duplication co-segregated with the phenotype and was absent in unaffected family members and control subjects. Coding and splice-site mutations of all annotated genes in the critical region were also excluded. The duplication partially overlaps with the reported duplications but has a different breakpoint. The most conserved 2.1 kb fragment in the duplication was cloned into the pGL3-promoter vector downstream of the firefly luciferase reporter gene in the 5' to 3' orientation and transfected into osteosarcoma U-2OS and Hela cells. A reduced luciferase activity was observed. CONCLUSION: The smallest duplication is described, which partially overlaps the reported duplications but has a different breakpoint, and its association with BDA2 in a Chinese family is confirmed. The results also provide evidence for cis-regulatory sequences in the duplication 3' of BMP2.
BACKGROUND:Brachydactyly type A2 (BDA2) is an autosomal dominant disorder. It was recently reported that a 5.9 kb duplication and a 5.5 kb duplication in the region 20p12.2-12.3 are associated with BDA2 in two European families. OBJECTIVE: To characterise a 6-generation Chinese family with 16 members affected by BDA2 and map the gene to 20p12.2-12.3. METHODS AND RESULTS: A 4.6 kb duplication downstream of the bone morphogenetic protein 2 (BMP2) was identified in the family. The duplication co-segregated with the phenotype and was absent in unaffected family members and control subjects. Coding and splice-site mutations of all annotated genes in the critical region were also excluded. The duplication partially overlaps with the reported duplications but has a different breakpoint. The most conserved 2.1 kb fragment in the duplication was cloned into the pGL3-promoter vector downstream of the firefly luciferase reporter gene in the 5' to 3' orientation and transfected into osteosarcomaU-2OS and Hela cells. A reduced luciferase activity was observed. CONCLUSION: The smallest duplication is described, which partially overlaps the reported duplications but has a different breakpoint, and its association with BDA2 in a Chinese family is confirmed. The results also provide evidence for cis-regulatory sequences in the duplication 3' of BMP2.
Authors: Tiong Yang Tan; Claudia Gonzaga-Jauregui; Elizabeth J Bhoj; Kevin A Strauss; Karlla Brigatti; Erik Puffenberger; Dong Li; LiQin Xie; Nanditha Das; Ioanna Skubas; Ron A Deckelbaum; Virginia Hughes; Susannah Brydges; Sarah Hatsell; Chia-Jen Siao; Melissa G Dominguez; Aris Economides; John D Overton; Valerie Mayne; Peter J Simm; Bryn O Jones; Stefanie Eggers; Gwenaël Le Guyader; Fanny Pelluard; Tobias B Haack; Marc Sturm; Angelika Riess; Stephan Waldmueller; Michael Hofbeck; Katharina Steindl; Pascal Joset; Anita Rauch; Hakon Hakonarson; Naomi L Baker; Peter G Farlie Journal: Am J Hum Genet Date: 2017-11-30 Impact factor: 11.025
Authors: Marcin Bednarek; Marek Trybus; Monika Kolanowska; Mateusz Koziej; Beata Kiec-Wilk; Artur Dobosz; Marta Kotlarek-Łysakowska; Anna Kubiak-Dydo; Ewelina Użarowska-Gąska; Julia Staręga-Rosłan; Paweł Gaj; Izabela Górzyńska; Katarzyna Serwan; Michał Świerniak; Adam Kot; Krystian Jażdżewski; Anna Wójcicka Journal: Mol Genet Genomic Med Date: 2021-01-24 Impact factor: 2.183
Authors: Xudong Liu; Linghan Gao; Aman Zhao; Rui Zhang; Baohu Ji; Lei Wang; Yonglan Zheng; Bingfang Zeng; Robert K Valenzuela; Lin He; Jie Ma Journal: PLoS One Date: 2014-04-07 Impact factor: 3.240