North Africa is defined as the geographical region separated from the rest of the continent by the Sahara and from Europe by the Mediterranean Sea. The main demographic features of North African populations are their familial structure and high rates of familial and geographic endogamy, which have a proven impact on health, particularly the occurrence of genetic diseases, with a greater effect on the frequency and spectrum of the rarest forms of autosomal recessive genetic diseases. More than 500 different genetic diseases have been reported in this region, most of which are autosomal recessive. During the last few decades, there has been great interest in the molecular investigation of large consanguineous North African families. The development of local capacities has brought a substantial improvement in the molecular characterization of these diseases, but the genetic bases of half of them remain unknown. Diseases of known molecular etiology are characterized by their genetic and mutational heterogeneity, although some founder mutations are encountered relatively frequently. Some founder mutations are specific to a single country or a specific ethnic or geographic group, and others are shared by all North African countries or worldwide. The impact of consanguinity on common multifactorial diseases is less evident.

Thalassemia is a disorder of hemoglobin (Hb) synthesis characterized by chronic hemolysis. In β-thalassemias major (β-TM), patients require regular transfusion at an early age due to severe anemia. Subsequently, intensive chelation therapy is initiated to mitigate the effects of the resultant iron overload. Clinical disease burden and the demanding treatment can affect health-related quality of life (HRQoL) outcomes in this population. The aim of this study was to assess HRQoL outcomes in Egyptian pediatric thalassemia patients. Patients were enrolled simultaneously from the hematology clinic at the National Research Institute in Cairo, Egypt. The Arabic version of SF36 tool was used to assess HRQoL outcomes. Socioeconomic data were collected by patient and parent interviews. Clinical data were collected by review of medical records. One hundred and thirty patients and 60 controls were enrolled, with a mean age of 5.4 ± 3.2 years and 6.3 ± 3.0, respectively. The HRQoL outcome scores were lower in all domains in the thalassemia group compared to the control group (p = 0.0001). Transfusion-dependent (TD) patients had lower HRQoL scores compared to nontransfusion-dependent (NTD) patients (p = 0.0001). Patient education and maternal education were independently associated with better HRQoL scores (p = 0.007, p = 0.028, respectively). Residents of rural areas reported lower scores compared to urban residents (p = 0.026). Thalassemia was associated with lower HRQoL scores, in all domains, compared to HRQoL in unaffected controls. Chronic transfusion independence, patient education, and maternal education were all associated with higher HRQoL scores. Psychological, social, and economic support for families with thalassemia are all essential tools to improve HRQoL outcomes.

PCNT encodes a large coiled-protein localizing to pericentriolar material and is associated with microcephalic osteodysplastic primordial dwarfism type II syndrome (MOPD II). We report our experience of nine new patients from seven unrelated consanguineous Egyptian families with the distinctive clinical features of MOPD II in whom a customized NGS panel showed homozygous truncating variants of PCNT. The NGS panel results were validated thereafter using Sanger sequencing revealing three previously reported and three novel PCNT pathogenic variants. The core phenotype appeared homogeneous to what had been reported before although patients differed in the severity showing inter and intra familial variability. The orodental pattern showed atrophic alveolar ridge (five patients), rootless tooth (four patients), tooth agenesis (three patients), and malformed tooth (three patients).In addition, mesiodens was a novel finding found in one patient. The novel c.9394-1G>T variant was found in two sibs who had tooth agenesis. CNS anomalies with possible vascular sequelae were documented in two male patients (22.2%). Simplified gyral pattern with poor development of the frontal horns of lateral ventricles was seen in four patients and mild thinning of the corpus callosum in two patients. Unilateral coronal craniosynstosis was noted in one patient and thick but short corpus callosum was an unusual finding noted in another. The later has not been reported before. Our results refine the clinical, neuroradiological, and orodental features and expand the molecular spectrum of MOPD II. K E Y W O R D S microcephalic osteodysplastic primordial dwarfism, MOPD II, orodental anomalies, PCNT, rootless teeth, tooth agenesis

Bone marrow failure syndromes (BMFS) are a group of disorders with complex pathophysiology characterized by a common phenotype of peripheral cytopenia and/or hypoplastic bone marrow. Understanding genetic factors contributing to the pathophysiology of BMFS has enabled the identification of causative genes and development of diagnostic tests. To date more than 40 mutations in genes involved in maintenance of genomic stability, DNA repair, ribosome and telomere biology have been identified. In addition, pathophysiological studies have provided insights into several biological pathways leading to the characterization of genotype/phenotype correlations as well as the development of diagnostic approaches and management strategies. Recent developments in bone marrow transplant techniques and the choice of conditioning regimens have helped improve transplant outcomes. However, current morbidity and mortality remain unacceptable underlining the need for further research in this area. Studies in mice have largely been unable to mimic disease phenotype in humans due to difficulties in fully replicating the human mutations and the differences between mouse and human cells with regard to telomere length regulation, processing of reactive oxygen species and lifespan. Recent advances in induced pluripotency have provided novel insights into disease pathogenesis and have generated excellent platforms for identifying signaling pathways and functional mapping of haplo‐insufficient genes involved in large‐scale chromosomal deletions–associated disorders. In this review, we have summarized the current state of knowledge in the field of BMFS with specific focus on modeling the inherited forms and how to best utilize these models for the development of targeted therapies. Stem Cells 2017;35:284–298

is a progressive genetic disease characterized by a neuroectodermal abnormality, mainly affecting the skin, nervous system, bones, eyes, and possibly other organs. This disorder has been divided into three forms: Neurofibromatosis type 1, Neurofibromatosis type 2, and Shwannomatosis (Jett & Friedman, 2010).Neurofibromatosis 1 (NF1; OMIM# 162200) is one of the most common autosomal dominant genetic diseases with a worldwide incidence of about 1:3500 (Jett & Friedman, 2010;Mao et al., 2018). In 95% of cases, clinical diagnosis