title: BiallelicSCN10Amutations in neuromuscular disease and epileptic encephalopathy.
abstract: Two consanguineous families, one of Sudanese ethnicity presenting progressive neuromuscular disease, severe cognitive impairment, muscle weakness, upper motor neuron lesion, anhydrosis, facial dysmorphism, and recurrent seizures and the other of Egyptian ethnicity presenting with neonatal hypotonia, bradycardia, and recurrent seizures, were evaluated for the causative gene mutation.
  
  
  
  Homozygosity mapping and whole exome sequencing (WES) identified damaging homozygous variants inSCN10A, namely c.4514C>T; p.Thr1505Met in the first family and c.4735C>T; p.Arg1579* in the second family. A third family, of Western European descent, included a child with febrile infection-related epilepsy syndrome (FIRES) who also had compound heterozygous missense mutations inSCN10A, namely, c.3482T>C; p.Met1161Thr and c.4709C>A; p.Thr1570Lys. A search forSCN10Avariants in three consortia datasets (EuroEPINOMICS, Epi4K/EPGP, Autism/dbGaP) identified an additional five individuals with compound heterozygous variants. A Hispanic male with infantile spasms [c.2842G>C; p.Val948Leu and c.1453C>T; p.Arg485Cys], and a Caucasian female with Lennox-Gastaut syndrome [c.1529C>T; p.Pro510Leu and c.4984G>A; p.Gly1662Ser] in the epilepsy databases and three in the autism databases with [c.4009T>A; p.Ser1337Thr and c.1141A>G; p.Ile381Val], [c.2972C>T; p.Pro991Leu and c.2470C>T; p.His824Tyr], and [c.4009T>A; p.Ser1337Thr and c.2052G>A; p.Met684Ile].
  
  
  
  SCN10Ais a member of the voltage-gated sodium channel (VGSC) gene family. Sodium channels are responsible for the instigation and proliferation of action potentials in central and peripheral nervous systems. Heterozygous mutations in VGSC genes cause a wide range of epileptic and peripheral nervous system disorders. This report presents autosomal recessive mutations inSCN10Athat may be linked to epilepsy-related phenotypes, Lennox-Gastaut syndrome, infantile spasms, and Autism Spectrum Disorder.
authors.affiliation: Pathology-Genetics Sidra Medical and Research Center Doha Qatar; Qatar Biomedical Research Institute Medical Genetics Center Hamad Bin Khalifa University Doha Qatar; Genetics Yale University School of Medicine New Haven Chicago.
authors.forename: Marios
authors.initials: M
authors.lastname: Kambouris
authors.affiliation: Centre de Génétique Hôpital d'Enfant Dijon France.
authors.forename: Julien
authors.initials: J
authors.lastname: Thevenon
authors.affiliation: Medical Genetics Branch National Human Genome Research Institute National Institutes of Health Bethesda Maryland; Undiagnosed Diseases Program National Human Genome Research Institute National Institutes of Health Bethesda Maryland.
authors.forename: Ariane
authors.initials: A
authors.lastname: Soldatos
authors.affiliation: Pediatrics University of Iowa Iowa City Iowa.
authors.forename: Allison
authors.initials: A
authors.lastname: Cox
authors.affiliation: Medical Genetics Branch National Human Genome Research Institute National Institutes of Health Bethesda Maryland.
authors.forename: Joshi
authors.initials: J
authors.lastname: Stephen
authors.affiliation: Clinical and Metabolic Genetics Pediatrics Hamad Medical Corporation Doha Qatar; Weill Cornell Medical College Doha Qatar.
authors.forename: Tawfeg
authors.initials: T
authors.lastname: Ben-Omran
authors.affiliation: Qatar Biomedical Research Institute Medical Genetics Center Hamad Bin Khalifa University Doha Qatar.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Al-Sarraj
authors.affiliation: Human Genetics University of Chicago Chicago Illinois.
authors.forename: Hala
authors.initials: H
authors.lastname: Boulos
authors.affiliation: Undiagnosed Diseases Program National Human Genome Research Institute National Institutes of Health Bethesda Maryland.
authors.forename: William
authors.initials: W
authors.lastname: Bone
authors.affiliation: Intramural Sequencing Center and Comparative Genomics Unit Genome Technology Branch National Genome Research Institute National Institutes of Health Bethesda Maryland.
authors.forename: James C
authors.initials: JC
authors.lastname: Mullikin
authors.affiliation: Centre de Génétique Hôpital d'Enfant Dijon France.
authors.forename: Alice
authors.initials: A
authors.lastname: Masurel-Paulet
authors.affiliation: Centre de Génétique Hôpital d'Enfant Dijon France.
authors.forename: Judith
authors.initials: J
authors.lastname: St-Onge
authors.affiliation: Centre de Génétique Hôpital d'Enfant Dijon France.
authors.forename: Yannis
authors.initials: Y
authors.lastname: Dufford
authors.affiliation: Centre de Génétique Hôpital d'Enfant Dijon France.
authors.forename: Corrine
authors.initials: C
authors.lastname: Chantegret
authors.affiliation: Centre de Génétique Hôpital d'Enfant Dijon France.
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.affiliation: Shafallah Medical Genetics Center Doha Qatar.
authors.forename: Jamil
authors.initials: J
authors.lastname: Al-Alami
authors.affiliation: Centre de Génétique Hôpital d'Enfant Dijon France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.affiliation: Centre de Génétique Hôpital d'Enfant Dijon France.
authors.forename: Jean Baptiste
authors.initials: JB
authors.lastname: Riviere
authors.affiliation: Medical Genetics Branch National Human Genome Research Institute National Institutes of Health Bethesda Maryland; Undiagnosed Diseases Program National Human Genome Research Institute National Institutes of Health Bethesda Maryland.
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.affiliation: Pediatrics University of Iowa Iowa City Iowa.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Bassuk
authors.affiliation: Undiagnosed Diseases Program National Human Genome Research Institute National Institutes of Health Bethesda Maryland.
authors.forename: May Christine V
authors.initials: MC
authors.lastname: Malicdan
authors.affiliation: Qatar Biomedical Research Institute Medical Genetics Center Hamad Bin Khalifa University Doha Qatar; Pediatrics University of Iowa Iowa City Iowa; Pediatrics University of Jordan Amman Jordan.
authors.forename: Hatem
authors.identifier: 0000-0001-6230-8316
authors.initials: H
authors.lastname: El-Shanti