Year 2022, Volume 5 - Issue 2

NA

Background: Physicians and geneticists face challenges in making accurate diagnoses during clinical evaluations; affecting patients and clinicians. The aim of this study was to estimate the hit rate of the non-consanguineous population. Moreover, prevalence of the genetic disorder in both the consanguineous and non- consanguineous population of Saudi Arabia at King Abdulaziz Medical City in Riyadh data. Methods: We reviewed 681 families and 1563 individuals with 2,565,335 variants in the King Abdullah International Medical Research Center (KAIMRC) Genomic Database (KGD), Riyadh, Saudi Arabia. All the ES requests were obtained from the physician and clinical geneticist of KAIMRC, and the test was performed either in-house or in a College of American Pathologists accredited laboratory center for clinical purposes. Results: A total of 151 non-consanguineous individuals with exome sequencing requests in the population genomic database of King Abdullah International Medical Research Center was considered for the study. In total, 27 had disease-causing variants, and the hit rate was 27/151 (18%). Among the 28 different variants in the 27 individuals, 50% were de novo variants and 50% inherited. The hit rate of the variants causing autosomal recessive disorders was 12/28 (42.8%), autosomal dominant disorders 13/28 (46.4%), and X-linked disorders 3/28 (10.7%). Conclusion: Non-consanguineous marriages have a lower risk of genetic disorders, and reducing consanguinity reduces the risk of genetic disorders by two to three times.

Background: The "autosomal recessive congenital ichthyosis (ARCI)" refers to a group of rare, heterogeneous, and non-syndromic disorders of keratinization, represented as abnormal scales over the entire body and attributable to defective epidermal keratinocyte differentiation and lipid metabolism. ARCI is caused by mutations in a wide variety of genes, including ABCA12, ALOX12B, ALOXE3, CYP4F22, NIPAL4, TGM1, CERS3, PNPLA1, CASP14, SDR9C7, and SULT2B1. The most common cause of ARCI is a TGM1 gene mutation, which is strongly associated with a collodion membrane at birth. Case presentation: A 15-year-old male patient presented with extensive scaling over the entire body since birth. His history revealed that he was born ash-colored in a membrane, kept in an incubator for one month, and clinically diagnosed with ichthyosis at birth. The patient, who had undergone no previous genetic testing, was subjected to whole exome sequencing with the preliminary diagnosis of autosomal recessive/X-linked recessive congenital ichthyosis. The analysis identified a homozygous c.1020delG change in the TGM1 gene in the form of a frameshift mutation that is classified as pathogenic according to the American College of Medical Genetics criteria. Conclusion: Next-generation sequencing technologies employing whole-exome sequencing enable the sequencing of all protein-coding DNA regions in a single run.

Background: NTRK2 is a group of neurological disorders characterized by epilepsy and developmental delay. Neurodevelopmental disorders and obesity are linked to various inherited disorders and are often missed or diagnosed late. Our aim was to review Obesity,hyperphagia,and developmental delay (OBHD) which it overlaps with a wide range of neurodevelopmental disorders with obesity. Also, variable expressivity can mislead the diagnosis, especially if there is a parent with a similar phenotype but a milder presentation. Case presentation: A 8 -year-old girl presented with 6-year history of increase wight. On Neurodevelopmental examination, she found to have a speech delay and autistic features. Parents deny sphincter dysfunction and cognitive delay. Family history was negative for members with a similar presentation. Genetic testing identified a novel mutation in NTKR2 gene. Parents were examined and underwent segregation analysis which came back negative, so it is de novo. Conclusion: Obesity and neurodevelopmental delay are features that are seen in a wide range of inherited disorders, either chromosomal or single-gene disorders. Here we highlight the importance of thorough history, examination, and the application of genetic testing sooner than later to avoid delaying the diagnosis and report a possible novel variant in the NTRK2 gene. Functional studies would be our next step.

Background: Phelan-McDermid syndrome (PMS) is a rare genetic condition caused by a heterozygous deletion in chromosome 22 in the 22q13 region or by a heterozygous pathogenic variant in SHANK3 gene. PMS is one of the important etiologies in children presenting mainly with intellectual delay, epilepsy, or autism spectrum disorder. Case Presentation: We describe a case of a 9-year-old male with a nonspecific neurodevelopmental disorder characterized by early signs of autism noticed from the age of 2 years. During his infancy, the patient exhibited slow gains of his milestones. He was later diagnosed with PMS and speech and intellectual disability. Conclusion: This study presented a novel case of a patient diagnosed with PMS in Saudi Arabia. Therefore, highlighting the clinical findings is essential to establish a common understanding of the disease. Patient education and awareness is a major part of the management plan since many families might require further explanation as they might need to deliver special education to their children affected by the syndrome. PMS is gaining great interest in research and patient awareness.

Not available