The imprinted expression of the IGF2 and H19 genes is controlled by the imprinting control region 1 (ICR1) located at chromosome 11p15.5. DNA methylation defects involving ICR1 result in two growth disorders with opposite phenotypes: an overgrowth disorder, the Beckwith-Wiedemann syndrome (maternal ICR1 hypermethylation in 10% of BWS cases) and a growth retardation disorder, the Silver-Russell syndrome (paternal ICR1 loss of methylation in 60% of SRS cases). In familial BWS, hypermethylation of ICR1 has been found in association with microdeletion of repetitive DNA motifs within ICR1 that bind the zinc finger protein CTCF; but more recently, ICR1 point mutations were described in BWS pedigrees. We present a case report of two brothers with BWS and prolonged post-pubertal growth resulting in very large stature. A maternally inherited point mutation was identified in ICR1 in both brothers, which altered binding of OCT transcription factors. The same mutation was present on the paternally inherited allele of their unaffected mother. This is a second report of a point mutation causing ICR1 hypermethylation by altering an OCT-binding motif. The atypical growth phenotype of the brothers may be connected to the unusual underlying cause of their BWS. arabic 24 English 118
Rebecca L Poole, Donald J Leith, Louise E Docherty, Mansur Ennuri Moftah Shmela, Christine Gicquel,, Miranda Splitt, I Karen Temple, Deborah J G Mackay(2-2012)

As little is known about the blood profile of camels in Libya, this article is the third of a 4-part series describing the biochemical and haematological blood profile in Libyan camels. In part 1 of these manuscripts, the overall blood biochemical and haematological mean values of camels in Libya were determined, parts 2-4 evaluate the effects of breed, gender and age respectively on these values. Blood samples were collected from 24 male and 42 female apparently healthy camels and the levels of enzymes, metabolites, electrolytes and haematological indices were measured. The blood of the male camels showed higher values of aspartate aminotransferase (AST), Lactate dehydrogenase (LDH), Amylase (AMS), total proteins, globulin and Phosphorus (Ph), than the female camels which showed higher values of glucose, Albumin/Globulin (A/G) ratio, urea, Iron (Fe), Calcium (Ca), Packed Cell volume (PCV), Haemoglobin (Hb), erythrocyte osmotic fragility, Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH), neutrophil and monocyte numbers. This study shows significant sex differences between male and female Libyan camels in many haematological and biochemical analytes. arabic 28 English 141
Anwar Mustafa Abdalhadi Abdalmula, Fathia mahmoud Mohammad Ashour, Mansur Ennuri Moftah Shmela, Fahima A Alnagar, Ismail M Abograra, Amal Omar Elarif Buker(1-2019)

The imprinted 11p15 region is organized in two domains, each of them under the control of its own imprinting control region (ICR1 for the IGF2/H19 domain and ICR2 for the KCNQ1OT1/CDKN1C domain). Disruption of 11p15 imprinting results in two fetal growth disorders with opposite phenotypes: the Beckwith-Wiedemann (BWS) and the Silver-Russell (SRS) syndromes. Various 11p15 genetic and epigenetic defects have been demonstrated in BWS and SRS. Among them, isolated DNA methylation defects account for approximately 60% of patients. To investigate whether cryptic copy number variations (CNVs) involving only part of one of the two imprinted domains account for 11p15 isolated DNA methylation defects, we designed a single nucleotide polymorphism array covering the whole 11p15 imprinted region and genotyped 185 SRS or BWS cases with loss or gain of DNA methylation at either ICR1 or ICR2. We describe herein novel small gain and loss CNVs in six BWS or SRS patients, including maternally inherited cis-duplications involving only part of one of the two imprinted domains. We also show that ICR2 deletions do not account for BWS with ICR2 loss of methylation and that uniparental isodisomy involving only one of the two imprinted domains is not a mechanism for SRS or BWS. arabic 22 English 137
- Demars, J., S. Rossignol, I. Netchine, K. S. Lee, Mansur Ennuri Moftah Shmela, L. Faivre, J. Weill, S. Odent, S. Azzi, P. Callier, J. Lucas, C. Dubourg, J. Andrieux, Y. Le Bouc, A. El-Osta , C. Gicquel(10-2011)