TY - JOUR
T1 - Variants in KIAA0825 underlie autosomal recessive postaxial polydactyly
AU - Ullah, Irfan
AU - Kakar, Naseebullah
AU - Schrauwen, Isabelle
AU - Hussain, Shabir
AU - Chakchouk, Imen
AU - Liaqat, Khurram
AU - Acharya, Anushree
AU - Wasif, Naveed
AU - Santos-Cortez, Regie Lyn P.
AU - Khan, Saadullah
AU - Aziz, Abdul
AU - Lee, Kwanghyuk
AU - Couthouis, Julien
AU - Horn, Denise
AU - Kragesteen, Bjørt K.
AU - Spielmann, Malte
AU - Thiele, Holger
AU - Nickerson, Deborah A.
AU - Bamshad, Michael J.
AU - Gitler, Aaron D.
AU - Ahmad, Jamil
AU - Ansar, Muhammad
AU - Borck, Guntram
AU - Ahmad, Wasim
AU - Leal, Suzanne M.
N1 - Funding Information:
Acknowledgements The authors would like to thank the family members who participated in this study. This work was supported by funds from the Higher Education Commission (HEC), Islamabad, Pakistan (to WA). A Georg Forster fellowship was provided by the Alexander von Humboldt Foundation (to NW). Genotyping and exome sequencing for family BD204 was provided by the University of Washington Center for Mendelian Genomics (UW-CMG) and was funded by the National Human Genome Research Institute and the National Heart, Lung and Blood Institute grant UM1 HG006493 (to DAN, MJB, and SML) and U24 HG008956. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Web Resources: ANNOVAR, http:// annovar.openbioinformatics.org/. Burrows-Wheeler Aligner (BWA), http://bio-bwa.sourceforge.net/. Combined Annotation Dependent Depletion (CADD), http://cadd.gs.washington.edu/. Gene Expression Ommibus (GEO), https://www.ncbi.nlm.nih.gov/geo/. Genome Aggregation Database (gnomAD), http://gnomad.broadinstitute.org/. Genome Analysis Toolkit (GATK), https://software.broadinstitute.org/ gatk/. ENCODE project, https://www.encodeproject.org/. Homozygosi-tyMapper, http://www.homozygositymapper.org/. International Mouse Phenotyping Consortium (IMPC), http://www.mousephenotype.org. Varbank pipeline v.2.3, https://varbank.ccg.uni-koeln.de/.
Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Postaxial polydactyly (PAP) is a common limb malformation that often leads to cosmetic and functional complications. Molecular evaluation of polydactyly can serve as a tool to elucidate genetic and signaling pathways that regulate limb development, specifically, the anterior-posterior specification of the limb. To date, only five genes have been identified for nonsyndromic PAP: FAM92A, GLI1, GLI3, IQCE and ZNF141. In this study, two Pakistani multiplex consanguineous families with autosomal recessive nonsyndromic PAP were clinically and molecularly evaluated. From both pedigrees, a DNA sample from an affected member underwent exome sequencing. In each family, we identified a segregating frameshift (c.591dupA [p.(Q198Tfs*21)]) and nonsense variant (c.2173A > T [p.(K725*)]) in KIAA0825 (also known as C5orf36). Although KIAA0825 encodes a protein of unknown function, it has been demonstrated that its murine ortholog is expressed during limb development. Our data contribute to the establishment of a catalog of genes important in limb patterning, which can aid in diagnosis and obtaining a better understanding of the biology of polydactyly.
AB - Postaxial polydactyly (PAP) is a common limb malformation that often leads to cosmetic and functional complications. Molecular evaluation of polydactyly can serve as a tool to elucidate genetic and signaling pathways that regulate limb development, specifically, the anterior-posterior specification of the limb. To date, only five genes have been identified for nonsyndromic PAP: FAM92A, GLI1, GLI3, IQCE and ZNF141. In this study, two Pakistani multiplex consanguineous families with autosomal recessive nonsyndromic PAP were clinically and molecularly evaluated. From both pedigrees, a DNA sample from an affected member underwent exome sequencing. In each family, we identified a segregating frameshift (c.591dupA [p.(Q198Tfs*21)]) and nonsense variant (c.2173A > T [p.(K725*)]) in KIAA0825 (also known as C5orf36). Although KIAA0825 encodes a protein of unknown function, it has been demonstrated that its murine ortholog is expressed during limb development. Our data contribute to the establishment of a catalog of genes important in limb patterning, which can aid in diagnosis and obtaining a better understanding of the biology of polydactyly.
UR - http://www.scopus.com/inward/record.url?scp=85064498777&partnerID=8YFLogxK
U2 - 10.1007/s00439-019-02000-0
DO - 10.1007/s00439-019-02000-0
M3 - Journal articles
C2 - 30982135
AN - SCOPUS:85064498777
SN - 0340-6717
VL - 138
SP - 593
EP - 600
JO - Human Genetics
JF - Human Genetics
IS - 6
ER -
