The imprinted expression of the IGF2 and H19 genes is controlled by the imprinting control region 1 (ICR1) located at chromosome 11p15.5. This methylation-sensitive chromatin insulator works by binding the zincfinger protein CTCF in a parent-specific manner. DNA methylation defects involving the ICR1 H19/IGF2 domain result in two growth disorders with opposite phenotypes: an overgrowth disorder, the Beckwith– Wiedemann syndrome (maternal ICR1 gain of methylation in 10% of BWS cases) and a growth retardation disorder, the Silver–Russell syndrome (paternal ICR1 loss of methylation in 60% of SRS cases). Although a few deletions removing part of ICR1 have been described in some familial BWS cases, little information is available regarding the mechanism of ICR1 DNA methylation defects. We investigated the CTCF gene and the ICR1 domain in 21 BWS patients with ICR1 gain of methylation and 16 SRS patients with ICR1 loss of methylation. We identified four constitutional ICR1 genetic defects in BWS patients, including a familial case. Three of those defects are newly identified imprinting defects consisting of small deletions and a single mutation, which do not involve one of the CTCF binding sites. Moreover, two of those defects affect OCT-binding sequences which are suggested to maintain the unmethylated state of the maternal allele. A single-nucleotide variation was identified in a SRS patient. Our data extends the spectrum of constitutive genetic ICR1 abnormalities and suggests that extensive and accurate analysis of ICR1 is required for appropriate genetic counseling in BWS patients with ICR1 gain of methylation.
Demars, J., Mansur Ennuri Moftah Shmela, S. Rossignol, J. Okabe, I. Netchine, S. Azzi, S. Cabrol, C. Le Caignec, A. David , Y. Le Bouc, A. El-Osta , C. Gicquel(9-2010)

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)

Abstract As little is known about the blood profile of camels in libya, this article is the second 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 evaluates the effects of breed, gender and age respectively on these values. Blood samples were collected from three camel breeds, namely, Fakhreya, Sirtaweya and Mahari, and the levels of enzymes, metabolites, electrolytes and haematological indices were measured. The blood of the Sirtaweya breed showed (i) higher levels of aspartate aminotransferase (AST), albumin and Phosphorus (Ph), than the other two breeds, (ii) higher levels of lactate dehydrogenase (LDH), amylase (AMS) and total proteins than the Fakhreya breed and (iii) higher levels of glucose, triglycerides, total cholesterol, Very Low Density Lipoprotein (VLDL), Low Density Lipoprotein (LDL), Calcium (Ca), Packed Cell volume (PCV), Mean Corpuscular Volume (MCV) and Albumin/Globulin (A/G) ratio than the Mahari breed. The Fakhreya breed had (i) higher levels of urea, Iron (Fe), Haemoglobin (Hb), Mean Corpuscular Haemoglobin (MCH) and neutrophils number than the other two breeds, (ii) higher levels of glucose, A/G, LDL, Ca, PCV, MCV and monocytes number than the Mahari breed and (iii) higher levels of erythrocyte osmotic fragility, MCH and Mean Corpuscular Hemoglobin Concentration (MCHC) than the Sirtaweya breed. The Mahari breed had (i) higher levels of globulin than the other two breeds, (ii) higher levels of AMS than the Fakhreya breed and (iii) higher levels of erythrocyte osmotic fragility, Erythrocyte Sedimentation Rate (ESR), MCHC than the Sirtaweya breed. The tested blood parameters in the three Libyan breeds in this study were affected by breed variations. arabic 28 English 143
Anwar Mustafa Abdalhadi Abdalmula, F. A. Alnagar, Amal Omar Elarif Buker, Fathia mahmoud Mohammad Ashour, I. M. Abograra , Mansur Ennuri Moftah Shmela(10-2018)