Preaxial polydactyly/triphalangeal thumb is associated with changed transcription factor-binding affinity in a family with a novel point mutation in the long-range cis-regulatory element ZRS
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Preaxial polydactyly/triphalangeal thumb is associated with changed transcription factor-binding affinity in a family with a novel point mutation in the long-range cis-regulatory element ZRS. / Farooq, Muhammad; Troelsen, Jesper T; Boyd, Mette; Eiberg, Hans; Hansen, Lars; Hussain, Muhammad Sajid; Rehman, Shoaib ur; Azhar, Aysha; Ali, Amjad; Bakhtiar, Syeda Marriam; Tommerup, Niels; Baig, Shahid Mahmood; Kjaer, Klaus W.
I: European Journal of Human Genetics, Bind 18, Nr. 6, 06.2010, s. 733-6.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Preaxial polydactyly/triphalangeal thumb is associated with changed transcription factor-binding affinity in a family with a novel point mutation in the long-range cis-regulatory element ZRS
AU - Farooq, Muhammad
AU - Troelsen, Jesper T
AU - Boyd, Mette
AU - Eiberg, Hans
AU - Hansen, Lars
AU - Hussain, Muhammad Sajid
AU - Rehman, Shoaib ur
AU - Azhar, Aysha
AU - Ali, Amjad
AU - Bakhtiar, Syeda Marriam
AU - Tommerup, Niels
AU - Baig, Shahid Mahmood
AU - Kjaer, Klaus W
PY - 2010/6
Y1 - 2010/6
N2 - A cis-regulatory sequence also known as zone of polarizing activity (ZPA) regulatory sequence (ZRS) located in intron 5 of LMBR1 is essential for expression of sonic hedgehog (SHH) in the developing posterior limb bud mesenchyme. Even though many point mutations causing preaxial duplication defects have been reported in ZRS, the underlying regulatory mechanism is still unknown. In this study, we analyzed the effect on transcription factor binding of a novel ZRS point mutation (463T>G) in a Pakistani family with preaxial polydactyly and triphalangeal thumb. Electrophoretical mobility shift assay demonstrated a marked difference between wild-type and the mutant probe, which uniquely bound one or several transcription factors extracted from Caco-2 cells. This finding supports a model in which ectopic anterior SHH expression in the developing limb results from abnormal binding of one or more transcription factors to the mutant sequence.
AB - A cis-regulatory sequence also known as zone of polarizing activity (ZPA) regulatory sequence (ZRS) located in intron 5 of LMBR1 is essential for expression of sonic hedgehog (SHH) in the developing posterior limb bud mesenchyme. Even though many point mutations causing preaxial duplication defects have been reported in ZRS, the underlying regulatory mechanism is still unknown. In this study, we analyzed the effect on transcription factor binding of a novel ZRS point mutation (463T>G) in a Pakistani family with preaxial polydactyly and triphalangeal thumb. Electrophoretical mobility shift assay demonstrated a marked difference between wild-type and the mutant probe, which uniquely bound one or several transcription factors extracted from Caco-2 cells. This finding supports a model in which ectopic anterior SHH expression in the developing limb results from abnormal binding of one or more transcription factors to the mutant sequence.
U2 - 10.1038/ejhg.2009.225
DO - 10.1038/ejhg.2009.225
M3 - Journal article
C2 - 20068592
VL - 18
SP - 733
EP - 736
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 6
ER -
ID: 20853132