Professor Samia Temtamy is a great Egyptian icon of human genetics and one of the first three most eminent international human genetics scientists who obtained a PhD degree in the aforementioned field. Prof. Temtamy had successfully laid the foundation for the science of human genetics and genomics at the National Research Centre shortly after the discovery of the correct number of human chromosomes and all the way to the human genome era. The story began more than 50 years ago with the establishment of a small unit at the National Research Centre in Cairo, Egypt. The unit started as a clinic that accepted patients with various inherited abnormalities. Later, that small unit became the Human Genetics Department in 1977. Prof. Temtamy had made a great effort to continue improving the services provided to patients with genetic disorders and the research facilities by converting the Human Genetics Department into the Division of Human Genetics and Genome Research that included several specialized departments in 2003. The Center of Excellence for Human Genetics was then established in 2014, which is considered the largest institute of human genetics in Egypt. This review summarizes the long journey taken and the great efforts put in by Prof. Temtamy and her team at the National Research Centre in the field of human genetics in Egypt, to keep pace with the continuous rapid advancement of human genetics and genomics and contribute to the international scientific community.

Sex determination and differentiation is a unique overly complex biological process controlled by a concerted action of a large network of genes, growth factors, hormones, and environmental determinants. The precise dosage and accurate spatial and temporal expression of those genes are essential for the normal sexual development. Recently, the advent of high-throughput technologies has greatly revolutionized our understanding of genetic pathways controlling sex development. Nevertheless, the condition is still highly challenging, and a small subset of patients receive a definitive molecular diagnosis. Large-scale collaborative basic science projects have been establishment, together with international registries for setting up standardized guidelines and diagnostic approaches that depend on careful clinical evaluation, hormonal and imaging analyses, and cytogenetic and molecular diagnostic tools. This review discusses the recent updates and how application of recent technologies in a stepwise fashion can significantly enhance the disorders of sexual development diagnostic rates and potentiate the management outcomes. Establishing a precise genetic diagnosis greatly affects the patient and family quality of life and allows for personalized management, predicting future risk and expected interventions, and provides better family counseling.

Background The etiological factors for early-onset infantile hypotonia with respiratory distress are variable. Spinal muscle atrophy with respiratory-distress type 1 (SMARD1) is usually presented with early-onset severe hypotonia and respiratory insufficiency that may require mechanical ventilation. Patients and methods Herein, we report on an Egyptian male infant who was born to nonconsanguineous parents, presented at the age of 2 months with acute onset of respiratory distress and severe hypotonia and required mechanical ventilatory support. As an expansion to the typical SMARD1 clinical features, hepatomegaly, elevated liver transaminases, and subdural hygroma were identified. Additionally, computed tomography chest showed pulmonary consolidation without evidence of diaphragmatic paralysis. The patient was mechanically ventilated and fed by nasogastric tube. There were multiple trials of extubation, which failed and tracheostomy was done. The patient died at the age of 11-month old. Whole-exome sequencing was done for the index patient and followed by variant filtration. Parental segregation was done to evaluate the phase of the detected variants. Results Whole-exome sequencing revealed two heterozygous variants in the immunoglobulin-binding protein 2 (IGHMBP2) gene, c.138 T>A and c.1616C>T, a pathogenic variant, and another of uncertain significance, respectively. In addition, a variant of uncertain significance was identified in CHRND gene (c.389 A>T). Biallelic IGHMBP2 variants are causative for SMARD1 and axonal Charcot–Marie–Tooth disease type 2S. Segregation study and clinical presentation prioritize the compound heterozygous variants in IGHMBP2 gene (c.138 T>A) and (c.1616C>T) as the causing disease molecular pathology. Conclusion Both SMARD1 and congenital myasthenic syndromes are possible genetic diagnoses for this patient. However, the clinical phenotype was more compatible with SMARD1. Nevertheless, the additional manifestations such as microcephaly, hepatomegaly, hypothyroidism, and neuroimaging were not featured in SMARD1.

Background Autism spectrum disorders (ASD) are considered one of the wide-ranging spectrums of neurodevelopmental disorders identified as 'pervasive developmental disorders,' which happen during the childhood. Evidence has been accumulating which suggests that immune system dysregulation is involved in the pathophysiology of autism. This study aims at investigating the serum levels of 16 cytokines in addition to CD4⁺ T cell count in patients with ASD. Patients and methods A multiplex assay for a panel of 16 cytokines and chemokines was applied to serum samples from 39 autistic patients and matched controls (n = 23) using Luminex technology. CD4⁺ T cell was estimated for all patients and controls using flow cytometry. Results Among a total of 16 analytes examined, the serum concentrations of monocyte chemoattractant protein-1/CCL2, receptor for advanced glycation end products, and growth-regulated oncogene-α (P = 0.03, 0.01, and 0.03, respectively) were significantly higher in ASD patients as compared with matched controls. However, the macrophage-inhibitory factor result showed significant downregulation (P = 0.008) in autistic patients compared with controls. In addition, CD4⁺ T cell count was significantly increased (P = 0.0002) in ASD patients in comparison with apparently healthy controls. Conclusion Children with ADS have significantly increased levels of monocyte chemoattractant protein-1/CCL2, growth-regulated oncogene-α, receptor for advanced glycation end products, and CD4⁺ T cell count, while macrophage-inhibitory factor was significantly decreased in comparison to controls, which suggests an underlying defect in the immune function and abnormal immune responses. These results may have intense implications for the treatment and diagnosis of ASD.

Background Nephropathic cystinosis (NC) (MIM #219800) is a rare autosomal recessive disorder that is characterized by accumulation of cystine in many tissues and organs, especially kidney and eyes. It occurs in ~1–2 of 100 000 live births. NC is caused by mutations in the CTNS gene encoding the lysosomal membrane transporter cystinosin. Cystinosin deficiency results in lysosomal cystine accumulation in different organs and systems. Cysteamine is the mainstay treatment to deplete the cystine accumulation. The aims were to establish white blood cell cystine measurement using mass spectrometry and evaluate the effect of treatment through measurement of some biochemical markers. Patients and methods The study included 15 patients with NC referred from the cystinosis outpatient clinic of Department of Pediatrics, Cairo University, over the period from June 2018 to January 2019 and 25 healthy normal participants as controls. Venous blood samples were taken for studying the effect of treatment through measurement of cystine level, chitotriosidase activity, thyroid profile, free carnitine, and acylcarnitine concentrations at two time points of evaluation. The basic evaluation was started in the beginning of June 2018, and the follow-up was started in the beginning of January 2019. Results Cystine concentration in 10 patients was decreased from the range of 4–13 to 2.3–8.5 nmol ½ cystine/mg proteins; eight patients had high activity of chitotriosidase (170–574 μmol/l/h), and then the activity range decreased to 90–371.5 μmol/l/h under treatment. One patient had high thyroid-stimulating hormone level (32 UI/ml), which was normalized to 12 UI/ml in the follow-up, and three patients had a high borderline thyroid-stimulating hormone level (20, 21, and 25.9 UI/ml) in the follow-up stage. Levels of free carnitine and acylcarnitine were normal at the two points of evaluation. Conclusion The current study draws attention to the importance of a follow-up policy, especially in Arabic countries, which have a high rate of consanguineous marriages.

Background Absence of teeth in the oral cavity is one of the most common dental abnormalities. Anodontia is a term used to describe congenitally missing teeth. It can manifest either as an isolated finding or as a part of a syndrome. Aim In this single-center 7-year retrospective study, we report and describe the most frequent genetic disorders associated with missing teeth in patients who presented to the outpatient clinic of Oro-dental Genetics Department at the National Research Center, Cairo, Egypt. Methods The recorded patients were classified into true anodontia and pseudoanodontia, which was further classified into primary pseudoanadontia and secondary pseudoanodontia. Results and conclusions The collected data showed that ectodermal dysplasia, followed by Ellis-van Creveld syndrome, was the most frequent disorder in the true anodontia group. Cleidocranial dysplasia was the most frequent disorder in the primary pseudoanodontia group, whereas Papillon–Lefèvre syndrome followed by congenital insensitivity to pain with anhidrosis and hypophosphatasia, was the most frequent genetic disorder in the secondary pseudoanodontia group.

Autism spectrum disorder (ASD) and achondroplasia are two distinctive disorders. Co-occurrence of ASD with different monogenic disorders, chromosomal aberration, and molecular defined syndromes has been reported. Yet, the coexistence of ASD with achondroplasia has been recently reported; it was supposed to be merely coincidental. It is of particular interest herein to report on an Egyptian patient having achondroplasia and ASD simultaneously. The current report includes a comparison of both cases and throws light on the importance of genetic and environmental contributions in the etiology of ASD.