title: Novel mutations in the genes TGM1 and ALOXE3 underlying autosomal recessive congenital ichthyosis.
abstract: BACKGROUND
  Ichthyoses are clinically characterized by scaling or hyperkeratosis of the skin or both. It can be an isolated condition limited to the skin or appear secondarily with involvement of other cutaneous or systemic abnormalities.
  
  
  METHODS
  The present study investigated clinical and molecular characterization of three consanguineous families (A, B, C) segregating two different forms of autosomal recessive congenital ichthyosis (ARCI). Linkage in three consanguineous families (A, B, C) segregating two different forms of ARCI was searched by typing microsatellite and single nucleotide polymorphism marker analysis. Sequencing of the two genes TGM1 and ALOXE3 was performed by the dideoxy chain termination method.
  
  
  RESULTS
  Genome-wide linkage analysis established linkage in family A to TGM1 gene on chromosome 14q11 and in families B and C to ALOXE3 gene on chromosome 17p13. Subsequently, sequencing of these genes using samples from affected family members led to the identification of three novel mutations: a missense variant p.Trp455Arg in TGM1 (family A); a nonsense variant p.Arg140* in ALOXE3 (family B); and a complex rearrangement in ALOXE3 (family C).
  
  
  CONCLUSIONS
  The present study further extends the spectrum of mutations in the two genes involved in causing ARCI. Characterizing the clinical spectrum resulting from mutations in the TGM1 and ALOXE3 genes will improve diagnosis and may direct clinical care of the family members.
authors.affiliation: Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Rahim
authors.initials: R
authors.lastname: Ullah
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.|Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ansar
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Zaka Ullah
authors.initials: ZU
authors.lastname: Durrani
authors.affiliation: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Kwanghyuk
authors.initials: K
authors.lastname: Lee
authors.affiliation: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Regie Lyn P
authors.initials: RL
authors.lastname: Santos-Cortez
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Dost
authors.initials: D
authors.lastname: Muhammad
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Mahboob
authors.initials: M
authors.lastname: Ali
authors.affiliation: Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Zia
authors.affiliation: Institute of Biochemistry, University of Baluchistan, Quetta, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ayub
authors.affiliation: Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Suliman
authors.initials: S
authors.lastname: Khan
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Josh D
authors.initials: JD
authors.lastname: Smith
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nickerson
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Shendure
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bamshad
authors.affiliation: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Leal
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000293:Adolescent; D002883:Chromosomes, Human, Pair 14; D002886:Chromosomes, Human, Pair 17; D018389:Codon, Nonsense; D003241:Consanguinity; D005260:Female; D015321:Gene Rearrangement; D005838:Genotype; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000235:genetics*; D017490:Ichthyosis, Lamellar / Q000235:genetics*; D008084:Lipoxygenase / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010154:Pakistan; D010375:Pedigree; D010641:Phenotype; D011503:Transglutaminases / Q000235:genetics*; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; C511051:ALOXE3 protein, human; D008084:Lipoxygenase; D011503:Transglutaminases; C105804:transglutaminase 1