Publications by authors named "Mohamed A Al-Muhaizea"

3 Publications

  • Page 1 of 1

Exome Sequencing: Mutilating Sensory Neuropathy with Spastic Paraplegia due to a Mutation in FAM134B Gene.

Case Rep Genet 2018 12;2018:9468049. Epub 2018 Dec 12.

Department of Neurology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Hereditary sensory and autonomic neuropathies (HSANs) are a clinically and genetically heterogeneous group of disorders involving various sensory and autonomic dysfunctions. The most common symptoms of HSANs include loss of sensations of pain and temperature that frequently lead to chronic ulcerations in the feet and hands of the patient. In this case study, we present the clinical features and genetic characteristics of two affected individuals from two unrelated Saudi families presenting mutilating sensory loss and spastic paraplegia. We employed homozygosity mapping and exome sequencing which is an efficient strategy to characterize the recessive genes, thus obtaining a rapid molecular diagnosis for genetically heterogeneous disorders like HSAN. Subsequently, a nonsense mutation (c.926 C>G; p.S309⁎) in was identified. In addition, we confirmed that the mutant FAM134B transcripts were reduced in these patients presumably disrupting the receptors of the degradative endoplasmic reticulum pathways that facilitate the autophagy processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/9468049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311306PMC
December 2018

Exome sequencing identifies novel NTRK1 mutations in patients with HSAN-IV phenotype.

Am J Med Genet A 2017 Apr;173(4):1009-1016

Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Hereditary sensory autonomic neuropathy type IV (HSAN-IV) is a rare autosomal recessive disorder that usually begins in infancy and is characterized by anhidrosis, insensitivity to noxious stimuli leading to self-mutilating behavior, and intellectual disability. HSAN-IV is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene, NTRK1, encoding the high-affinity receptor of nerve growth factor (NGF) which maps to chromosome 1q21-q22. Patients with HSAN-IV lack all NGF-dependent neurons, the primary afferents and sympathetic postganglionic neurons leading to lack of pain sensation and the presence of anhidrosis, respectively. Herein, we report nine patients from nine unrelated families with HSAN-IV due to various mutations in NTRK1, five of which are novel. These are three missense and two nonsense mutations distributed in various domains of NTRK1 involved in binding of NGF. The affected patients had variable intellectual deficits, and some had delayed diagnosis of HSAN-IV. In addition to being the first report of HSAN-IV from the Arabian Peninsula, this report expands the mutational spectrum of patients with NTRK1 mutations and provides further insights for molecular and clinical diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.38120DOI Listing
April 2017

Clinical and pathological heterogeneity of a congenital disorder of glycosylation manifesting as a myasthenic/myopathic syndrome.

Neuromuscul Disord 2014 Apr 4;24(4):353-9. Epub 2014 Jan 4.

Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Saudi Arabia; Department of Neuroscience, King Faisal Specialist Hospital and Research Centre, Saudi Arabia.

Congenital disorders of glycosylation are often associated with muscle weakness in apparent isolation or as part of a multi-systemic disorder. We report here the clinical and pathological features resulting from a homozygous mutation of ALG2 in an extended family. Phenotypic heterogeneity is observed among the small cohort of patients reported to date and is highlighted by our study. Linkage analysis, homozygozity mapping and whole exome sequencing followed clinical and pathological characterization of patients who presented with a congenital limb girdle pattern of weakness with no ocular or bulbar involvement. Nerve stimulation studies were consistent with a congenital myasthenic syndrome. Severity and progression of disease was variable. Muscle biopsies showed myopathic features, ragged red fibers and a sub-sarcolemmal accumulation of structurally normal mitochondria. Whole exome sequencing revealed an indel mutation c.214_224delGGGGACTGGCTdelinsAGTCCCCG, p.72_75delGDWLinsSPR in exon 1 of ALG2. Mutation of ALG2 manifested as a limb girdle pattern of muscle weakness with defects at both the neuromuscular junction and sarcomere. In addition the accumulation and distribution of mitochondria in the diseased muscle and the presence of ragged red fibers were supportive of a mitochondrial myopathy. ALG2 mutation results in a heterogeneous phenotype and care should be taken in categorization and treatment of these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nmd.2013.12.010DOI Listing
April 2014