title: Association of AHSG with alopecia and mental retardation (APMR) syndrome.
abstract: Alopecia with mental retardation syndrome (APMR) is a very rare autosomal recessive condition that is associated with total or partial absence of hair from the scalp and other parts of the body as well as variable intellectual disability. Here we present whole-exome sequencing results of a large consanguineous family segregating APMR syndrome with seven affected family members. Our study revealed a novel predicted pathogenic, homozygous missense mutation in the AHSG (OMIM 138680) gene (AHSG: NM_001622:exon7:c.950G>A:p.Arg317His). The variant is predicted to affect a region of the protein required for protein processing and disrupts a phosphorylation motif. In addition, the altered protein migrates with an aberrant size relative to healthy individuals. Consistent with the phenotype, AHSG maps within APMR linkage region 1 (APMR 1) as reported before, and falls within runs of homozygosity (ROH). Previous families with APMR syndrome have been studied through linkage analyses and the linkage resolution did not allow pointing out to a single gene candidate. Our study is the first report to identify a homozygous missense mutation for APMR syndrome through whole-exome sequencing.
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Reza Sailani
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Jahanbani
authors.affiliation: Child Growth and Development Research Center, Pediatrics Department, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Jafar
authors.initials: J
authors.lastname: Nasiri
authors.affiliation: Medical Genetic Laboratory of Genome, Isfahan, Iran.
authors.forename: Mahdiyeh
authors.initials: M
authors.lastname: Behnam
authors.affiliation: Division of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran.|Medical Genetics Laboratory, Isfahan University Hospital, Isfahan, Iran.
authors.forename: Mansoor
authors.initials: M
authors.lastname: Salehi
authors.affiliation: Medical Genetics Laboratory, Isfahan University Hospital, Isfahan, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Sedghi
authors.affiliation: Medical Genetics Laboratory, Isfahan University Hospital, Isfahan, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Hoseinzadeh
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: Amin
authors.initials: A
authors.lastname: Zia
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Gruber
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: Janet Linnea
authors.initials: JL
authors.lastname: Lynch
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lam
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: Juliane
authors.initials: J
authors.lastname: Winkelmann
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: Semira
authors.initials: S
authors.lastname: Amirkiai
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: Baoxu
authors.initials: B
authors.lastname: Pang
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Rego
authors.affiliation: Clinic of Internal Medicine, Department of Cardiology, University Heart Center, Jena University Hospital, Jena, Germany.
authors.forename: Safoura
authors.initials: S
authors.lastname: Mazroui
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bernstein
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA. mpsnyder@stanford.edu.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Snyder
mesh_terms: D000505:Alopecia / Q000235:genetics*; D000595:Amino Acid Sequence; D015153:Blotting, Western; D003241:Consanguinity; D059472:Exome; D005260:Female; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010766:Phosphorylation; D060749:alpha-2-HS-Glycoprotein / Q000737:chemistry / Q000235:genetics*
chemical_list: C556354:AHSG protein, human; D060749:alpha-2-HS-Glycoprotein