Behnam et al. page.1
Short communication
A novel missense mutation in HSF4, responsible for autosomal recessive congenital
cataract
Mahdiyeh Behnam1*, Eri Imagawa2*, Ahmad Reza Salehi Chaleshtori3, Firooze Ronasian1,
Mansoor Salehi4, Noriko Miyake2, Naomichi Matsumoto2
*These authors were equally responsible for the work described in this paper
1
Medical Genetics Laboratory of Genome, Isfahan, Iran
2
Department of Human Genetics, Yokohama City University Graduate School of Medicine,
Yokohama, Japan
3
Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University,
Tehran, Iran
4
Division of Genetics and Molecular Biology, School of Medicine, Isfahan University of
Medical Sciences, Isfahan, Iran
Correspondence to Dr Naomichi Matsumoto, or Dr Noriko Miyake, Department of Human
Genetics, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ku,
Yokohama
2360004,
Japan:
naomat@yokohama-cu.ac.jp
nmiyake@yokohama-cu.ac.jp (N. Miyake)
(N.
Matsumoto)
or
Behnam et al. page.2
Supplementary methods
Whole Exome Sequencing
Whole exome sequencing was performed in the affected individual (VI-2 in Figure 1a) as
previously reported.1, 2 Briefly, 3 μg of genomic DNA was sheared to 200 bp using a Covaris S2
system (Covaris, Woburn, MA, USA). Genome partitioning was performed using a SureSelect
Human All Exon Kit v5 (Agilent Technologies, Santa Clara, CA, USA). The prepared libraries
were sequenced on a HiSeq2000 (Illumina, San Diego, CA, USA) with 101-bp paired-end reads
with 7-bp index reads. Both reads were aligned to the human reference genome hg19 using
Novoalign 3.00 (http://www.novocraft.com). The aligned reads were then processed by Picard
software (http://picard.sourceforge.net) to remove polymerase chain reaction duplicates. The
variants were called using the Genome Analysis Toolkit 1.6-5 (GATK;
http://www.broadinstitute.org/gatk) with the GATK Best Practice Variant Detection v3
recommendations (http://www.broadinstitute.org/gatk/guide/best-practices) and annotated by
ANNOVAR (2012Mar08, http://www.openbioinformatics.org/annovar). Using these criteria,
only variants located in the coding region and the adjacent 2-bp were extracted and common
variants registered in dbSNP build 137 (Minor allele frequency ≥ 0.01)
(http://genome.ucsc.edu/cgi-bin/hgTrackUi?hgsid=316787363&g=snp137Common&hgTracksC
onfigPage=configure) were excluded.
The pathogenic effects of all candidate variants were predicted using SIFT (http://sift.jcvi.org),
Polyphen2 (http://genetics.bwh.harvard.edu/pph2/) and MutationTaster
(http://www.mutationtaster.org/) softwares.
Behnam et al. page.3
Supplemental table.1 Summary of 86 known genes whose mutations found in cataract
Gene
Ref accession
Gene
No.
Ref accession
Gene
No.
Ref accession
No.
ABCA3
NM_ 001089
EFNA5
NM_001962
MYH9
NM_002473
ABHD12
NM_001042472
EPHA2
NM_004431
NHS
NM_198270
ADAM9
NM_003816
ERCC2
NM_000400
OCRL
NM_000276
ADAMTS18
NM_199355
EYA1
NM_000503
OPA3
NM_001017989
AGK
NM_018238
FAM126A
NM_032581
PAX6
NM_001127612
AKR1E2
NM_001040177
FAR1
NM_032228
PITX3
NM_005029
BEST1
NM_004183
FOXE3
NM_012186
POLG
NM_002693
BFSP1
NM_001195
FTL
NM_000146
PVRL3
NM_015480
BFSP2
NM_003571
FYCO1
NM_024513
PXDN
NM_012293
BMP4
NM_001202
GALK1
NM_000154
RNLS
NM_001031709
CHMP4B
NM_176812
GCNT2
NM_145655
RYR1
NM_000540
CLPB
NM_030813
GEMIN4
NM_015721
SC5D
NM_006918
COL4A1
NM_001845
GFER
NM_005262
SIX5
NM_175875
CRYAA
NM_000394
GJA3
NM_021954
SLC16A12
NM_213606
CRYAB
NM_001885
GJA8
NM_005267
SLC16A2
NM_006517
CRYBA1
NM_005208
GSTM1
NM_000561
SLC33A1
NM_004733
CRYBA2
NM_057093
GSTT1
NM_000853
SLURP1
NM_020427
CRYBA4
NM_001886
HSF4
NM_001538
TDRD7
NM_014290
CRYBB1
NM_001887
HSF4b
NM_001040667
TFR2
NM_003227
CRYBB2
NM_000496
IDO1
NM_002164
TMEM114
NM_001146336
CRYBB3
NM_004076
JAM3
NM_032801
TMEM70
NM_017866
CRYGB
NM_005210
KCNJ13
NM_002242
TRPM3
NM_001007471
CRYGC
NM_020989
LIM2
NM_030657
UCHL1
NM_004181
CRYGD
NM_006891
MAF
NM_001044671
UNC45B
NM_173167
CRYGS
NM_017541
MED13
NM_005121
VIM
NM_003380
CTDP1
NM_004715
MFSD6L
NM_152599
VSX2
NM_182894
CYP1B1
NM_000104
MIP
NM_012064
WFS1
NM_00600
CYP51A1
NM_00114615
MIR184
NR_029705
WRN
NM_000553
DNM2
NM_00100536
MVK
NM_000431
Registered genes in Human Gene Mutation Database (HGMD, Professional release 2015.1,
http://www.hgmd.org)
Behnam et al. page.4
Supplementary references
1.
Saitsu H, Nishimura T, Muramatsu K, et al. De novo mutations in the autophagy gene
WDR45 cause static encephalopathy of childhood with neurodegeneration in adulthood.
Nat Genet 2013;45: 445-9, 449e1.
2.
Imagawa E, Osaka H, Yamashita A, et al. A hemizygous GYG2 mutation and Leigh
syndrome: a possible link? Hum Genet 2014;133: 225-34.