Background Disruption of 11p15 imprinting results in two fetal growth disorders with opposite phenotypes: the Beckwith–Wiedemann (BWS; MIM 130650) and the Silver–Russell (SRS; MIM 180860) syndromes. DNA methylation defects account for 60% of BWS and SRS cases and, in most cases, occur without any identified mutation in a cis-acting regulatory sequence or a trans-acting factor. Methods We investigated whether 11p15 cis-acting sequence variants account for primary DNA methylation defects in patients with SRS and BWS with loss of DNA methylation at ICR1 and ICR2, respectively. Results We identified a 4.5 kb haplotype that, upon maternal transmission, is associated with a risk of ICR2 loss of DNA methylation in patients with BWS. This novel region is located within the second intron of the KCNQ1 gene, 170 kb upstream of the ICR2 imprinting centre and encompasses two CTCF binding sites. We showed that, within the 4.5 kb region, two SNPs (rs11823023 and rs179436) affect CTCF occupancy at DNA motifs flanking the CTCF 20 bp core motif. Conclusions This study shows that genetic variants confer a risk of DNA methylation defect with a parent-of-origin effect and highlights the crucial role of CTCF for the regulation of genomic imprinting of the CDKN1C/KCNQ1 domain. arabic 26 English 132
Julie Demars, Mansur Ennuri Moftah Shmela, Abdul Waheed Khan , Kai Syin Lee, Salah Azzi, Patrice Dehais, Irène Netchine, Sylvie Rossignol, Yves Le Bouc, Assam El-Osta, Christine Gicquel(7-2014)

Carpal conformation is thought to contribute to the frequency of carpal pathology so non-invasive measurement of carpal morphometry would be useful to identify joints at risk. However, there are scant radiographic morphometrical details for the carpals of Thoroughbred (TB) and Standardbred (SB) racehorses even though these breeds differ in the incidence of carpal damage. This study aimed to identify morphometrical similarities and differences in carpal conformation in TB and SB. Thirty carpal dorsopalmar radiographs (DP) were collected from 15 TB and 15 SB. All DP radiographs were at zero degrees or within the acceptable range of rotation. Twelve carpal radiographic parameters were selected and measured on each radiograph. Statistical analysis found significant differences in four carpal parameters. These parameters revealed that the middle carpal joint in SB was significantly more angled distomedially whereas the radial distal metaphysis showed a greater distolateral inclination in TB. The radiocarpal and the carpometacarpal articulations exhibited common features in the two groups of horses. These carpal traits in TB and SB highlight their potential association with loading distribution and pathology. Measuring carpi from untrained and injured horses is necessary to establish breed specific features for the ideal carpal conformation in each of these breeds.
Aiman Hussein Saleh Oheida, Abdulrhman Mohamed Salah Alrtib, Aiman Abdulghader Salim Shalgum, Mansur Ennuri Moftah Shmela, Mohamed A Marzok, Helen M S Davies(4-2019)

The 11p15 region is organised into two independent imprinted domains controlled by imprinting control regions, which carry opposite germline imprints. Dysregulation of 11p15 genomic imprinting results in two human fetal growth disorders (Silver-Russell syndrome (SRS, MIM 180860) and Beckwith-Wiedemann syndrome (BWS, MIM 130650)) with opposite growth phenotypes. The mouse orthologous region on distal chromosome 7 (dist7) is well conserved in its organisation and its regulation. Targeted mutagenesis in mice has provided highly valuable clues in terms of the mechanisms involved in the regulation of genomic imprinting of the 11p15/dist7 imprinted region. On the other hand, the recent identification of unexpected genetic defects in BWS and SRS patients also brought new insights into the mechanisms of 11p15 imprinting regulation. However, some mouse models and human genetic defects show contradictions in term of growth phenotypes and parental transmission. In this review, we extensively analyse those various mouse and human models and more particularly models with mutations affecting the two imprinting centres, in order to improve our understanding of regulation of 11p15/dist7 genomic imprinting. arabic 21 English 117
Mansur Ennuri Moftah Shmela, C. F. Gicquel(1-2013)