Mini Review
Volume 11 Issue 4 - 2022
Does RNA and Whole Genome Sequencing Help in Identification of Ultra Rare Degenerative Diseases in Children?
Ahmed Abdalla Bashir*
Pediatrics, Genetics, Clinical Studies Scientist, Al Mana Group, Saudi Arabia and UCLA, USA
*Corresponding Author: Ahmed Abdalla Bashir, Pediatrics, Genetics, Clinical Studies Scientist, Al Mana Group, Saudi Arabia and UCLA, USA.
Received: January 10, 2022; Published: March 31, 2022


Neurodevelopmental disorders [NDDs] occur due to errors in the biological processes in the maturation and development of the nervous system [1]. NDDs include autism spectrum disorder [ASD], intellectual disability, attention deficit hyperactivity disorder [ADHD], schizophrenia, and bipolar disorder [2]. The medical global estimate prevalence of autism, intellectual disability and schizophrenia are: 62/10,000, 10.37/1000, and 4/1000 respectively [3].

NDDs are frequently due to genetic mutations and can be detected with whole exome sequencing [WES]. In Almana General Hospitals Saudi Arabia, we are frequently confronted with seriously disabling cases of NDDs in children. Even with extensive use of methods of genetic diagnostic tools we fail to reach a molecular genetics diagnosis.

Novel causal mutations can be identified using an approach such as WES [4]. Multiple genetic defects, like GRM7, STX1A, CCAR2, EEF1D, GALNT2, SLC44A1, LRRIQ3, AMZ2, CLMN, SEC23IP, INIP, NARG2, FAM234B, and TRAP1, were identified using WES method [5]. Continuum model gradient hypothesis showed that schizophrenia shares origin of disturbance of brain cells as seen in intellectual disability, ASD, and ADHD.

We propose here a prospective cohort experimental study by a mechanism by collecting blood and punch of the skin biopsy for detection and identification of causal mutations of NDDs. RNA sequencing [RNA Seq] followed by whole genome sequencing [WGS] will be used to develop models that will improve the utility of test in enhancing our ability to diagnose each family mutations. The goals will be:

  1. This will lead to a determination of the mutation diagnostic pattern in the index patient and his/her family.
  2. It will also allow screening of future pregnancies, through a chorionic villous sampling at 11 - 14 weeks age of pregnancy [6] or amniocentesis at 15 - 20 weeks of pregnancy [7], enabling the family to decide whether to continue or not with the pregnancy if ever the fetus is affected.

The study population will include consanguineous families who have child/children diagnosed with a neurodegenerative disease. Skin biopsies and blood samples will be collected from these individuals affected by the disorder and their family members. DNA obtained from blood samples will be used to assess changes in DNA sequences, or to perform tests to look at differences in proteins, enzymes, and cell types in blood. Skin cells will be used to create Induced Pluripotent Stem Cells [iPSCs], Inducible Differentiated Reprogrammed Muscle [iDRM] cells, fibroblast cells, that can be induced to create different cell lines. For example, for muscular dystrophy, these cells will be induced to create muscle-like cells. The obtained cells will be stored in a repository (bank) and made available for use in future research.

We expect to identify the genetic cause of rare NDDs among children seen in the Eastern province of Saudi Arabia. If successful the identification of the genetic mutation seen in diagnosing each family condition will lead to the creation of possible treatments like gene therapy in order to solve their underlying genetic disease.

Keywords: Induced Pluripotent Stem Cells [iPSCs]; Inducible Differentiated Reprogrammed Muscle [iDRM]; Neurodevelopmental Disorders [NDDs]; Autism Spectrum Disorder [ASD]; Attention Deficit Hyperactivity Disorder [ADHD]


  1. Stiles J and Jernigan TL. “The basics of brain development”. Neuropsychology Review 4 (2010): 327-348.
  2. Sur M and Rubenstein JL. “Patterning and plasticity of the cerebral cortex”. Science5749 (2005): 805-810.
  3. Bishop KM., et al. “Distinct actions of Emx1, Emx2, and Pax6 in regulating the specification of areas in the developing neocortex”. Journal of Neuroscience 17 (2002): 7627-7638.
  4. Al-Mubarak B., et al. “Whole exome sequencing reveals inherited and de novo variants in autism spectrum disorder: a trio study from Saudi families”. Scientific Reports 1 (2017): 5679.
  5. Reuter MS., et al. “Diagnostic yield and novel candidate genes by exome sequencing in 152 consanguineous families with neurodevelopmental disorders”. JAMA Psychiatry 3 (2017): 293-299.
  8. Hane Lee., et al. “Clinical exome sequencing for genetic identification of rare Mendelian Disorders”. JAMA 18 (2014): 1800-1887.
  9. Hennery M Adam. “Degenerative Central Nervous System (CNS) Disease”. Pediatrics in Review5 (2001): 175-176.
  10. Shi L., et al. “Long-read sequencing and de novo assembly of a Chinese genome”. Nature Communications 7 (2016): 12065.
  11. “ORFfinder”. www.ncbi.nlm.
  12. “ORFpredictor”.
  13. Pan Q., et al. “Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing”. Nature Genetics 12 (2008): 1413-1415.
  14. Al Mubarak., et al. “Whole exome sequencing reveals inherited and de novo variant in autism spectrum disorder: a trio study from Saudi families”. Scientific Reports 1 (2017): 5679.
  15. Sreekantam S and Wassmer E. “An approach to developmental regression”. Pediatrics and Child Health6 (2013): 273-277.
Citation: Ahmed Abdalla Bashir. “Does RNA and Whole Genome Sequencing Help in Identification of Ultra Rare Degenerative Diseases in Children?”. EC Paediatrics 11.4 (2022): 82-87.

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