Year 2018, Volume 1 - Issue 1

No abstract available

C-terminal tensin-like (cten, also known as tensin4, TNS4) is the fourth member of the tensin family. all tensin family members localizes in focal adhesion sites. Cten shares the sequence homology with other tensins at its C-terminal region by having the SH2 and PTB domains. Cten is expressed in some normal tissue such as prostate and placenta while down-regulated in prostate cancer. The overexpression of cten was found associates with tumors of breast, colon, lung, stomach, skin and pancreas. It interacts with growth factors and cytokines as regulators. Also it has been found that cten expression promotes cell motility and enhances tumorigenicity. The collective findings support that cten is having a role in carcinogenesis and promising biomarker. It can be a candidate for a therapeutic target for solid cancers.

Syndactyly (Syn = together; Dactylos = digits) is the most common limb defect mostly characterized by webbing of digits. It may be webbing with or without bony fusion and inherited mostly in autosomal dominant manner, although also reported as autosomal recessive, X-linked or isolated entity. It also shows diverse clinical and phenotypic heterogeneity and mostly observed as unilateral or bilateral and symmetrical or asymmetrical forms. Syndactyly mostly occurs either as an isolated anomaly or as a part of a complex syndrome (+150 syndromes). Here, non-syndromic syndactyly has been classified according to genetic and molecular basis. The non-syndromic syndactyly has been classified into nine different types. Up till now, the major genes identified to cause hereditary syndactyly are mainly involved in the sonic hedgehog pathway and zone of polarizing activity. The present review mostly focuses on summarizing the recent advances in molecular genetics, including known genes and loci responsible for non-syndromic syndactyly. The present review will contribute to the understanding of the pathogenesis underlying non-syndromic and syndromic syndactyly, improving clinical and molecular diagnosis; thus, making genetic counseling and prenatal testing easier in future. Keywords: Limb malformation, syndactyly, digit webbing, molecular genetics.

Human kidneys serve important physiological functions in the body. There is an increasing evidence suggesting that the majority of renal diseases have an underlying genetic component. At least 40 genes have been shown to be involved in kidney development and many more genes are expressed within the kidney and regulate renal physiology. It is observed that genetic and congenital disorders are more common in Arab countries than in industrialized countries. Saudi Arabia is the largest Arab country and estimation of patients with end-stage kidney failure is 136 for each million yearly. Preliminary observations indicate that children in Saudi Arabia probably have a higher incidence of polycystic kidney disease, familial juvenile nephronophthisis, congenital urological anomalies, and familial nephrotic syndrome. Molecular diagnosis would help enormously in prevention and introduce early management which could ensure a better outcome. This is a review article of molecular studies conducted in the Kingdom of Saudi Arabia from 1990 till present time to elucidate disease-causing genes of inherited kidney disease.

Background: Measurement of branched-chain amino acids (BCAAs) [valine (Val), alloisoleucine (allo-Ile), isoleucine (Ile), and leucine (Leu)] in plasma and dry blood spot samples is important for the diagnosis and monitoring of maple syrup urine disease (MSUD), which is a metabolic disorder that affects metabolism of BCAAs. We used a temporally short program on an High performance liquid chromatography (HPLC) (Biochrom 30) for the first time in Saudi Arabia to analyze plasma samples for the diagnosis of MSUD. Methodology: 500 μl of plasma were mixed with 500 μl of 10% sulphosalicylic acid, followed by shaking for 5-10 seconds on a vortexer. The mixture was incubated at 4 C for 10 minutes followed by centrifugation at 10,000 rpm for 5 minutes. Supernatants were transferred into HPLC vials for injection. Results: For all amino acids, the limit of detection and limit of quantification were 5.0 and 10.0 μmol/l, respectively. The method was linear in the range of 10-2,500 μmol/l. The method was specific and selective for the detection of BCAAs, including alloisoleucine. The correlation coefficient (CV) of method comparison was greater than 0.980 and percent recovery of all amino acids in plasma was 80%-100%, which was evaluated at two amino acid concentrations. Precision was assessed by repeat analysis of spiked plasma samples and percent CV was found to be

Background: Next-generation sequencing has been leading the genetic study of human disease for the past 10 years, generating a huge amount of sequence variant data, which are stored in variant call format (VCF) files. The aim of the study was to reassess the utility of VCF files for reanalysis. Methodology: This is a descriptive observational study of Saudi patients with undiagnosed genetic conditions. VCF files from 20 samples were referred to the molecular laboratory by physicians for reanalysis using variant interpretation software. Results: Seven cases (n = 20) have been reported differently from the outside laboratory. This accounts for almost 35% of all cases and is mainly due to the ability to gather more information about the patient's phenotype. One whole-genome sequence (WGS) case changed from inconclusive to negative. In addition, we identified variants related to the patient's phenotype in six cases; two of them were WGS and four were whole-exome sequence, all reported as negative before the reanalysis. Conclusion: Comprehensive phenotyping of individuals is a crucial step in identifying candidate phenotype-related variants. We outline the benefit obtained from access to the patient's medical records and communication with referring physicians.

Background: Microcephalic osteodysplastic primordial dwarfism (MOPD) is a wide spectrum of monogenic disorders with several subtypes and numerous genes have been identified. It is characterized by the significant pre- and post-natal growth retardation, severe short stature (dwarfism), and microcephaly. MOPD type II (MIM# 210720) is a recessive disease, which is the first mapped MOPD caused by mutations in PCNT (605925) gene encoding pericentrin protein, in chromosome 21q22. In contrast, Klinefelter syndrome (KS; XXY syndrome) is a known numerical chromosomal disorder that is considered the most frequent sex chromosomal with no or minimal physical features before puberty. Affected children may have tall stature and subtle intellectual disabilities, speech delay, and evolving psychosocial dysfunctions. Case Presentation: We present a 3-year-old dwarf child with the facial and physical finding of MOPD. Interestingly, his karyotype revealed 47;XXY abnormality. While searching for the main cause for his dwarf phenotype, gene testing for PCNT gene showed pathogenic homozygous mutation with both parents proved to be heterozygous for the same mutation. Conclusion: While the karyotype proved the 47;XXY syndrome, the clinical phenotype of MOPD caused by PCNT leads his physical array and dominated the patient's facial profile. Early diagnosis for both syndromes is essential in order to offer early treatment for the complications or to provide an appropriate counseling and intervention if needed.

Background: Periventricular nodular heterotopia, a common form of neuronal heterotopia, is heterogeneous in etiology. Recessive mutations in ARFGEF2 causing microcephaly and periventricular heterotopia have rarely been reported. Case Presentation: We report two Saudi siblings with a homozygous ARFGEF2 mutation (c.958 + 1G > A) presenting with microcephaly, dyskinetic movements, seizures, and a distinct brain magnetic resonance imaging pattern, describing the genotype and radiology phenotype correlation. Conclusion: We speculate that the involvement of the putamen may be a key under recognized feature of ARFGEF2 mutations.

Background: LAMA1 gene is mutated in patients with Poretti-Boltshauser syndrome, which include mainly the characteristic neuroimaging findings of cerebellar dysplasia and cysts. Case Presentation: We present a novel homozygous LAMA1 variant that is predicted to cause atypical phenotype of severe arthrogryposis, feeding difficulties, developmental delay, retinopathy, and no cerebellar involvement. Conclusion: Our findings are suggestive of absence of cerebellar involvement in LAMA1 mutations in some cases and phenotype may include severe arthrogryposis.

Background: PPM1D gene encodes for metal-dependent protein phosphatase. Its function includes the inhibition of some tumor suppressor genes, DNA damage response, and cell cycle control. Germline heterozygous de novo mutations in this gene were reported to cause intellectual disability and hypotonia. Case Presentation: We report a 40-month-old girl with an intractable seizure disorder, microcephaly, and global developmental delay. She had frequent epileptiform discharges on electroencephalography. Molecular investigations showed a homozygous truncating mutation in the PPM1D gene. Both parents were healthy heterozygous carriers. Conclusion: This is the first time in the literature to describe a homozygous biallelic mutation in the PPM1D gene, which resulted in epileptic encephalopathy, microcephaly, and global developmental delay. PPM1D mutations could be inherited as autosomal recessive with asymptomatic heterozygote carriers.