Human Genetics

, Volume 136, Issue 3, pp 287–296

Association of AHSG with alopecia and mental retardation (APMR) syndrome

  • M. Reza Sailani
  • Fereshteh Jahanbani
  • Jafar Nasiri
  • Mahdiyeh Behnam
  • Mansoor Salehi
  • Maryam Sedghi
  • Majid Hoseinzadeh
  • Shinichi Takahashi
  • Amin Zia
  • Joshua Gruber
  • Janet Linnea Lynch
  • Daniel Lam
  • Juliane Winkelmann
  • Semira Amirkiai
  • Baoxu Pang
  • Shannon Rego
  • Safoura Mazroui
  • Jonathan A. Bernstein
  • Michael P. Snyder
Original Investigation

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.

Supplementary material

439_2016_1756_MOESM1_ESM.docx (19 kb)
Supplementary material 1 (DOCX 18 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • M. Reza Sailani
    • 1
  • Fereshteh Jahanbani
    • 1
  • Jafar Nasiri
    • 3
  • Mahdiyeh Behnam
    • 5
  • Mansoor Salehi
    • 4
    • 6
  • Maryam Sedghi
    • 6
  • Majid Hoseinzadeh
    • 6
  • Shinichi Takahashi
    • 1
  • Amin Zia
    • 1
  • Joshua Gruber
    • 1
  • Janet Linnea Lynch
    • 1
  • Daniel Lam
    • 1
  • Juliane Winkelmann
    • 1
  • Semira Amirkiai
    • 1
  • Baoxu Pang
    • 1
  • Shannon Rego
    • 1
  • Safoura Mazroui
    • 7
  • Jonathan A. Bernstein
    • 2
  • Michael P. Snyder
    • 1
  1. 1.Department of GeneticsStanford UniversityStanfordUSA
  2. 2.Department of PediatricsStanford UniversityStanfordUSA
  3. 3.Child Growth and Development Research Center, Pediatrics DepartmentIsfahan University of Medical SciencesIsfahanIran
  4. 4.Division of Genetics and Molecular BiologyIsfahan University of Medical SciencesIsfahanIran
  5. 5.Medical Genetic Laboratory of GenomeIsfahanIran
  6. 6.Medical Genetics LaboratoryIsfahan University HospitalIsfahanIran
  7. 7.Clinic of Internal Medicine, Department of CardiologyUniversity Heart Center, Jena University HospitalJenaGermany

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