The Diagnostic Value of Whole-Exome Sequencing in a Spectrum of Rare Neurological Disorders Associated with Cerebellar Atrophy.

Several neurological disorders, neurodevelopmental disorders, and neurodegenerative disorders have a genetic element with various clinical presentations ranging from mild to severe presentation. Neurological disorders are rare multifactorial disorders characterized by dysfunction and degeneration of synapses, neurons, and glial cells which are essential for movement, coordination, muscle strength, sensation, and cognition. The cerebellum might be involved at any time, either during development and maturation or later in life.

Chromosome 9p terminal deletion in nine Egyptian patients and narrowing of the critical region for trigonocephaly.

Background: This study aimed to delineate the clinical phenotype of patients with 9p deletions, pinpoint the chromosomal breakpoints, and identify the critical region for trigonocephaly, which is a frequent finding in 9p terminal deletion.

Methods: We investigated a cohort of nine patients with chromosome 9p terminal deletions who all displayed developmental delay, intellectual disability, hypotonia, and dysmorphic features. Of them, eight had trigonocephaly, seven had brain anomalies, seven had autistic manifestations, seven had fair hair, and six had a congenital heart defect (CHD).

Interstitial Deletion of 2q22.2q22.3 Involving the Entire Gene in a Case of Mowat-Wilson Syndrome.

Mowat-Wilson syndrome (MWS) is a rare autosomal dominant syndrome characterized by dysmorphic features, mental retardation, and congenital heart disease (CHD). MWS results from microdeletions of chromosome 2q23 or de novo SNVs involving the gene. Here, we report on an Egyptian MWS patient diagnosed by chromosomal microarray (CMA).

Advances in genomic diagnosis of a large cohort of Egyptian patients with disorders of sex development.

Disorders/differences of sex development (DSD) comprise a group of congenital disorders that affect the genitourinary tract and usually involve the endocrine and reproductive system. The aim of this work was to identify genetic variants responsible for disorders of human urogenital development in a cohort of Egyptian patients. This three-year study included 225 patients with various DSD forms, referred to the genetic DSD and endocrinology clinic, National Research Centre, Egypt.

Phenotypic and Molecular Cytogenetic Analysis of a Case of Monosomy 1p36 Syndrome due to Unbalanced Translocation.

Monosomy 1p36 syndrome is one of the most common submicroscopic deletion syndromes, which is characterized by the presence of delayed developmental milestones, intellectual disability, and clinically recognizable dysmorphic craniofacial features. The syndrome comprises 4 cytogenetic groups including pure terminal deletions, interstitial deletions, complex rearrangements, and derivative chromosomes 1 due to unbalanced translocations, where unbalanced translocations represent the least percentage of all cases of monosomy 1p36 (7%). Most patients with monosomy 1p36 due to an unbalanced translocation can be cytogenetically diagnosed using conventional techniques.

Clinical and genetic characterization of ten Egyptian patients with Wolf-Hirschhorn syndrome and review of literature.

Background: Wolf-Hirschhorn syndrome (WHS) (OMIM 194190) is a multiple congenital anomalies/intellectual disability syndrome. It is caused by partial loss of genetic material from the distal portion of the short arm of chromosome.

Methods: We studied the phenotype-genotype correlation.

Cytogenetic Spectrum of Ovotesticular Difference of Sex Development (OT DSD) among a Large Cohort of DSD Patients and Literature Review.

Ovotesticular difference of sex development (OT DSD) is a rare genetic disorder with an incidence of about 1/100,000 live births. The majority of OT DSD patients show a 46,XX karyotype, others may have 46,XX/46,XY chimerism or exhibit various mosaic sex chromosome combinations, and less commonly they may have a 46,XY karyotype. The aim of this work is to report the clinical, pathological, and karyotypic variations in OT DSD patients diagnosed among a large cohort of DSD patients.

Testis formation in XX individuals resulting from novel pathogenic variants in Wilms' tumor 1 () gene.

Sex determination in mammals is governed by antagonistic interactions of two genetic pathways, imbalance in which may lead to disorders/differences of sex development (DSD) in human. Among 46,XX individuals with testicular DSD (TDSD) or ovotesticular DSD (OTDSD), testicular tissue is present in the gonad. Although the testis-determining gene is present in many cases, the etiology is unknown in most -negative patients.

Unbalanced 14;X Translocation and Pattern of X Inactivation in a Female Patient with Multiple Congenital Anomalies.

We report on a female patient who was first evaluated at the age of 6 years with developmental delay, dysmorphic facial features, seizures, and autistic behavior. A brain CT showed complete agenesis of the corpus callosum, and EEG recorded bilateral epileptogenic foci. Karyotype analysis revealed 45,X,psu dic(14;X)(p11;p22).

Clinical and Cytogenetic Study of Egyptian Patients with Sex Chromosome Disorders of Sex Development.

Disorders of sex development (DSD) are conditions with an abnormal development of chromosomal, gonadal, or anatomical sex. Sex chromosome DSD involve conditions associated with either numerical or structural abnormalities of the sex chromosomes. This study included patients comprising a wide spectrum of presenting features suggestive of DSD and aimed at studying the frequency of sex chromosome abnormalities among 108 Egyptian DSD patients who presented to the Clinical Genetics and Endocrinology Clinics, National Research Centre (NRC) over the 2-year period of 2013 and 2014.

Genotoxic Effects Due to Exposure to Chromium and Nickel Among Electroplating Workers.

Using chromium and nickel for electroplating is important in many industries. This process induces variable adverse health effects among exposed workers. The aim of this study is to detect the genotoxic effects of combined exposure to chromium and nickel among electroplating workers.

WT1 Gene Mutation, p.R462W, in a 46,XY DSD Patient from Egypt with Gonadoblastoma and Review of the Literature.

WT1 gene mutations have been described in 46,XY patients with ambiguous genitalia or complete gonadal dysgenesis with or without Wilms' tumor, nephropathy, gonadoblastoma, and other defects, e.g., cryptorchidism or hypospadias.

Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015) : Jeddah, Kingdom of Saudi Arabia. 30 November - 3 December 2015.

O1 Regulation of genes by telomere length over long distances Jerry W. Shay O2 The microtubule destabilizer KIF2A regulates the postnatal establishment of neuronal circuits in addition to prenatal cell survival, cell migration, and axon elongation, and its loss leading to malformation of cortical development and severe epilepsy Noriko Homma, Ruyun Zhou, Muhammad Imran Naseer, Adeel G. Chaudhary, Mohammed Al-Qahtani, Nobutaka Hirokawa O3 Integration of metagenomics and metabolomics in gut microbiome research Maryam Goudarzi, Albert J.

Identification of NR5A1 Mutations and Possible Digenic Inheritance in 46,XY Gonadal Dysgenesis.

The phenotypic spectrum of patients carrying NR5A1 mutations ranges from 46,XY gonadal dysgenesis to male infertility. Phenotypic variability could be due to digenic or oligogenic inheritance of pathogenic variants in other testis-determining genes. Here, exome sequencing identified 2 pathogenic de novo NR5A1 mutations in 2 patients with 46,XY gonadal dysgenesis, p.

Mutational Profile of 10 Afflicted Egyptian Families with 17-β-HSD-3 Deficiency.

This study aimed at the detection of HSD17B3 gene mutations in Egyptian patients with suspected diagnosis of 46,XY DSD due to 17-β-HSD-3 deficiency and at evaluation of phenotype/genotype relationship of these mutations. The study was conducted on 11 patients of 10 families which were provisionally diagnosed to have 17-β-HSD-3 enzyme deficiency. Karyotyping, hormonal evaluation of testosterone, x0394;4-androstenedione, and dihydrotestosterone, and sequencing analysis of the 11 exons of the HSD17B3 gene were done.

Genotype/phenotype correlation in a female patient with 21q22.3 and 12p13.33 duplications.

Many chromosomal rearrangements that lead to copy-number gains or losses have been shown to cause distinctive and recognizable clinical phenotypes. Conventional cytogenetic analysis can detect many, but not all, rearrangements depending on its power of resolution. The wide use of whole-genome array-based comparative genomic hybridization (array-CGH) techniques has allowed the detection of novel syndromes and to establish genotype-phenotype correlations by delineating at high resolution the regions involved in specific chromosomal aberrations.

Sex Chromosome Mosaicism in the Gonads of DSD Patients: A Karyotype/Phenotype Correlation.

Sex chromosome mosaicism results in a large clinical spectrum of disorders of sexual development (DSD). The percentage of 45,X cells in the developing gonad plays a major role in sex determination. However, few reports on the gonadal mosaic status have been published, and the phenotype is usually correlated with peripheral lymphocyte karyotypes, which makes the phenotype prediction imprecise.

A novel mutation (c.2735_2736delTC) in the androgen receptor gene in 46,XY females with complete androgen insensitivity syndrome in an Egyptian family.

Background: Androgen insensitivity syndrome (AIS) results from resistance of the target tissues to the effect of the androgenic hormones producing a phenotype with varying degrees of feminization ranging from male infertility to completely normal female external genitalia. Androgen receptor (AR) is a transcription factor that interacts with the androgenic steroids that act as ligands activating the AR, and via different cellular mechanisms, the activated AR binds to the DNA of target tissues to induce the desired biological changes. To date, more than 800 different mutations in the AR gene have been identified in patients with AIS and the majority of these mutations are localized in the ligand-binding domain.

Analysis of the gene coding for steroidogenic factor 1 (SF1, NR5A1) in a cohort of 50 Egyptian patients with 46,XY disorders of sex development.

Objective: Steroidogenic factor 1 (SF1, NR5A1) is a key transcriptional regulator of genes involved in the hypothalamic-pituitary-gonadal axis. Recently, SF1 mutations were found to be a frequent cause of 46,XY disorders of sex development (DSD) in humans. We investigate the frequency of NR5A1 mutations in an Egyptian cohort of XY DSD.

Isodicentric Y chromosomes in Egyptian patients with disorders of sex development (DSD).

Isodicentric chromosome formation is the most common structural abnormality of the Y chromosome. As dicentrics are mitotically unstable, they are subsequently lost during cell division resulting in mosaicism with a 45,X cell line. We report on six patients with variable signs of disorders of sex development (DSD) including ambiguous genitalia, short stature, primary amenorrhea, and male infertility with azoospermia.