Antimicrobial resistance and ESBL profile of Uropathogens among pregnant women at Edna Adan Hospital, Hargeisa, Somaliland.

Background: The emergence and spread of antimicrobial resistance (AMR) among uropathogens is increasing, especially in resource limited settings due to a number of reasons. The production of Extended Spectrum β-Lactamase (ESBL) by some strains of E. coli and methicillin resistant Staphylococcus species, limits the choice of antimicrobials in the treatment of urinary tract infection (UTI) globally.

A mutation in the major autophagy gene, WIPI2, associated with global developmental abnormalities.

We describe a large consanguineous pedigree from a remote area of Northern Pakistan, with a complex developmental disorder associated with wide-ranging symptoms, including mental retardation, speech and language impairment and other neurological, psychiatric, skeletal and cardiac abnormalities. We initially carried out a genetic study using the HumanCytoSNP-12 v2.1 Illumina gene chip on nine family members and identified a single region of homozygosity shared amongst four affected individuals on chromosome 7p22 (positions 3059377-5478971).

A missense mutation in TRAPPC6A leads to build-up of the protein, in patients with a neurodevelopmental syndrome and dysmorphic features.

Childhood onset clinical syndromes involving intellectual disability and dysmorphic features, such as polydactyly, suggest common developmental pathways link seemingly unrelated phenotypes. We identified a consanguineous family of Saudi origin with varying complex features including intellectual disability, speech delay, facial dysmorphism and polydactyly. Combining, microarray based comparative genomic hybridisation (CGH) to identify regions of homozygosity, with exome sequencing, led to the identification of homozygous mutations in five candidate genes (RSPH6A, ANKK1, AMOTL1, ALKBH8, TRAPPC6A), all of which appear to be pathogenic as predicted by Proven, SIFT and PolyPhen2 and segregate perfectly with the disease phenotype.

Whole-exome sequencing reveals a recurrent mutation in the cathepsin C gene that causes Papillon-Lefevre syndrome in a Saudi family.

Papillon-Lefevre syndrome (PALS) is a rare, autosomal recessive disorder characterized by periodontitis and hyperkeratosis over the palms and soles. Mutations in the cathepsin C gene (CTSC) have been recognized as the cause of PALS since the late 1990s. More than 75 mutations in CTSC have been identified, and phenotypic variability between different mutations has been described.

A Novel Missense Mutation in the CLPP Gene Causing Perrault Syndrome Type 3 in a Turkish Family.

Perrault syndrome (PRLTS) is a heterogeneous group of clinical and genetic disorders characterized by sensory neuronal hearing loss in both sexes and premature ovarian failure or infertility in females. Neurological and hearing loss symptoms appear early in life, but female infertility cannot be detected before puberty. Spastic limbs, muscle weakness, delayed puberty and irregular menstrual cycles have also been observed in PRLTS patients.

A novel homozygous PTH1R variant identified through whole-exome sequencing further expands the clinical spectrum of primary failure of tooth eruption in a consanguineous Saudi family.

Objectives: The present study aimed to identify the genetic cause of non-syndromic primary failure of tooth eruption in a five-generation consanguineous Saudi family using whole-exome sequencing (WES) analysis.

Design: The family pedigree and phenotype were obtained from patient medical records. WES of all four affected family members was performed using the 51 Mb SureSelect V4 library kit and then sequenced using the Illumina HiSeq2000 sequencing system.

The alkylglycerol monooxygenase (AGMO) gene previously involved in autism also causes a novel syndromic form of primary microcephaly in a consanguineous Saudi family.

Autosomal recessive primary microcephaly (MCPH) refers to a genetically heterogeneous group of neurodevelopmental disorders in which patients exhibit a marked decrease in occipitofrontal head circumference at birth and a variable degree of intellectual disability. To date, 18 genes have been reported for MCPH worldwide. We enrolled a consanguineous family from Saudi Arabia presenting with primary microcephaly, developmental delay, short stature and intellectual disability.

BRAF gene: From human cancers to developmental syndromes.

The BRAF gene encodes for a serine/threonine protein kinase that participates in the MAPK/ERK signalling pathway and plays a vital role in cancers and developmental syndromes (RASopathies). The current review discusses the clinical significance of the BRAF gene and other members of RAS/RAF cascade in human cancers and RAS/MAPK syndromes, and focuses the molecular basis and clinical genetics of BRAF to better understand its parallel involvement in both tumourigenesis and RAS/MAPK syndromes-Noonan syndrome, cardio-facio-cutaneous syndrome and LEOPARD syndrome.

Truncating mutation in intracellular phospholipase A₁ gene (DDHD2) in hereditary spastic paraplegia with intellectual disability (SPG54).

Background: Hereditary spastic paraplegias (HSP), a group of genetically heterogeneous neurological disorders with more than 56 documented loci (SPG1-56), are described either as uncomplicated (or pure), or complicated where in addition to spasticity and weakness of lower extremeties, additional neurological symptoms are present, including dementia, loss of vision, epilepsy, mental retardation and ichthyosis. We identified a large consanguineous family of Indian descent with four affected members with childhood onset HSP (SPG54), presenting with upper and lower limb spasticity, mental retardation and agenesis of the corpus callosum.

Results: A common region of homozygosity on chromosome 8 spanning seven megabases (Mb) was identified in the affected individuals using the Illumina human cytoSNP-12 DNA Analysis BeadChip Kit.

Identification of Two Homozygous Sequence Variants in the COL7A1 Gene Underlying Dystrophic Epidermolysis Bullosa by Whole-Exome Analysis in a Consanguineous Family.

Dystrophic epidermolysis bullosa (DEB) is an inherited skin disorder with variable severity and heterogeneous genetic involvement. Diagnostic approaches for this condition include clinical evaluations and electron microscopy of patients' skin biopsies, followed by Sanger sequencing (SS) of a large gene (118 exons) that encodes the alpha chain of type VII collagen (COL7A1) located on Chromosome 3p21.1.

Exome analysis identified a novel missense mutation in the CLPP gene in a consanguineous Saudi family expanding the clinical spectrum of Perrault Syndrome type-3.

Perrault syndrome (PRLTS) is a clinically and genetically heterogeneous disorder. Both male and female patients suffer from sensory neuronal hearing loss in early childhood, and female patients are characterized by premature ovarian failure and infertility after puberty. Clinical diagnosis may not be possible in early life, because key features of PRLTS, for example infertility and premature ovarian failure, do not appear before puberty.

Case of Sjögren-Larsson syndrome with a large deletion in the ALDH3A2 gene confirmed by single nucleotide polymorphism array analysis.

Sjögren-Larsson syndrome (SLS) is a neurocutaneous disorder inherited in an autosomal recessive fashion. SLS patients are characterized by lipid metabolism error, primarily leading to cardinal signs of ichthyosis, spasticity and mental retardation. Additional signs include short stature, epilepsy, retinal abnormalities and photophobia.

Novel nonsense mutation in the PTRF gene underlies congenital generalized lipodystrophy in a consanguineous Saudi family.

Congenital generalized lipodystrophies (CGLs) are a heterogeneous group of rare, monogenic disorders characterized by loss of sub-cutaneous fat, muscular hypertrophy, acanthosis nigricans, hepatomegaly, cardiac arrhythmias, impaired metabolism and mental retardation. Four different but overlapping phenotypes (CGL1-4) have been identified, which are caused by mutations in AGPAT2 at 9q34.3, BSCL2 at 11q13, CAV1 at 7q31.

First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene.

GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them.

An identification and prediction methods for feature-subsets of CpG islands methylation based on human peripheral blood leukocytes of chromosome 21q.

The pace of technology has allowed classification of feature-subset of methylated and unmethylated of CpG islands of DNA sequence properties. As methylation of CpG islands is involved in various biological phenomena and function of the DNA methylation is correlated to various human diseases such as cancer, analysis of the CpG islands has become important and useful in characterizing and modelling biological phenomena and understanding mechanism of such diseases. However, analysis of the data associated with the CpG islands is a quite new and challenging subject in bioinformatics, systems biology and epigenetics.