Supplementary Table 1. Primers used to amplify DKC1

Name / Forward Primer / Reverse Primer / Amplicon Size (bp)
DKC1 exon 6 / TCTTTCCCACATCATCACCA / GCTGGAATAAGGCACCTGTC / 463
DKC1 exon 7 / TTTTGTCCCCTTTTCAGTCG / TTTCAACTCCAGCAGAAGCA / 455
DKC1 exon 9 / GGCACCTACATTCGGACATT / AACAATAAAAAGAGCAAGCCTCA / 1055
DKC1 exon15 / CGAGTGCCTTTAGTGCTTCC / CAGACAGCTGCGGACAGTTA / 712
DKC1 3’UTR-1 / CGGTGATGTTACCTGGTGTG / GCTTTGAGGAAGTGCAAAGG / 423
DKC1 3’UTR-2 / GTTTGAGTTGGGAAGCCTCA / CAACAAGAAAACCCAACAGGA / 503
DKC1 3’UTR-3 / TGATGGGCCTGGTAGTTTTC / GCCTCTGAGTACTTGATCTCACAT / 423
DKC1 start / CAACCTCTCCGAGCTTCAAC / AGCCTGCAGCCCTTACCT / 533
DKC1promoter / TGCCTTTAGCCAGACCTAGA / AGTACGGAGGGCGAGACC / 1268

Supplementary Table 2. Primersused to amplify flanking sequences 9 kb upstream and 1.1 kb downstream of DKC1

Name / Forward Primer / Reverse Primer / Amplicon Size (bp)
5’-1 DKC / AGTACGGAGGGCGAGACC / GGGAATTAGATGAGGCACCA / 856
5’-2 DKC / TCTGCCTTGAATCACCACAA / TACAGCAAGCCAGGAGCTTT / 861
5’-3 DKC / GACACTCAGTGGGCCATTTT / CGAGGAATTTGGCTGTCATT / 884
5’-4 DKC / GAACATGGGGAATGACTGCT / CTTCTTGGTCCAGGCATCAC / 804
5’-5 DKC / GCCTGGACCAAGAAGCCTAT / CCTCTCCAGCTGACTTCCAG / 880
5’-6 DKC / CTGGAAGTCAGCTGGAGAGG / TGCAACAAAAATGGCATGAT / 983
5’-10 DKC / TGCACCTTTGTCAAAAACCA / TGCCCAAAATTGGTCAGGTA / 995
5’-11 DKC / TGACCAATTTTGGGCAATTT / CAGGGGGCTATGTTGATTTG / 830
5’-12 DKC / TCAGGCTGTGATTCGAACTG / AGTGGCAGCTGAAGTTCCAT / 877
5’-13 DKC / TGGCAAAGTCTGAATGCTTG / TCACTTGTCGAGAGCCACA / 895
5’-14 DKC / AGCTCATCACCCTGAAGCAT / ACCCAGGGTCACGAGAAAG / 806
Gap1 DKC / CCTGGCTAGATGTGGTGAAAA / TGTGAAGGTTCTTGACCCAAA / 274
Gap2 DKC / CAGAGTTGAGGTGGGGAATG / TAACAGAGCCCCAGTTTTGG / 453
Gap3 DKC / GGCATCCATAAACGACTTCTC / AGGCATATTGGCATGTAGCC / 406
Gap4 DKC / TTGCAAGGTTGCAGGATACA / TGGGCTCAAGTGATCTTCCT / 526
Gap5 DKC / TCTTTGGGACCTACGACCTG / CACGCCCAGCTAATTTTTGT / 584
Gap6 DKC / GACAAGCTACAGACTGGGAGAAA / GGAGTGCAATGGCTCAATCT / 528
Gap7 DKC / AGATTGAGCCATTGCACTCC / CACTTGGGCCTTTCTGTCAT / 440
Gap8 DKC / GAGGCTGCAGTGAGATGTGA / GATCGAGACCATCCTGGCTA / 573
Gap9 DKC / AGGTTCACGCCATTCTCC / CTCAGGACCTCCAAAGCAAG / 423
3’ DKC / TGTGCCCTCTTGTTTTAGGC / AGCTCCTGGACAACAGCATT / 1155

Supplementary Table 3. Clinical features of affected family members

Individual / Sex / Age* / Classic Features / Pulmonary and Liver Manifestations** / Other History
II.10 / M / (d.30) / Hyperpigmentation / Lung disease/”scarring”
Cirrhosis
III.4 / M / (d.17) / Nail dystrophy Hyperpigmentation / Lung disease
Cirrhosis
III.9 / M / (d.51) / Nail dystrophy Hyperpigmentation / IPF/UIP with BOOP
III.10 / M / (d.39) / Nail dystrophy Hyperpigmentation / Possible Lung disease
Cirrhosis
III.12 / M / (d.39) / Nail dystrophy Hyperpigmentation / Clubbing / Possible heart attack
III.14 / M / (d.34) / Absent Nails
Oral leukoplakia / Chronic Cough / Metastatic squamous
cell carcinoma (skin)
III.18 / M / (d.43) / Hyperpigmentation
Oral leukoplakia / Lung disease
III.22 / M / (d.40) / Hyperpigmentation / IPF/UIP with BOOP
V.2 / M / 17 / Nail dystrophy / Very short telomeres
V.4 / M / 14 / Nail dystrophy / Very short telomeres
V.5 / M / 16 / Very short telomeres
V.6 / M / 10 / Hyperpigmentation / Very short telomeres
Diabetes

* Age in parentheses refers to age at the time of death

**IPF refers to idiopathic pulmonary fibrosis, UIP refers to usual interstitial pneumonia, BOOP refers to bronchiolitis obliterans organizing pneumonia

Supplementary Table 4. LOD scores and information content by position at Xq28

Marker / Position in cM (DeCode) / Position
(HG18) / MultipointLOD / MultipointInformation Content / Singlepoint
LOD / Singlepoint
Information Content
rs1539270 / 140.51 / 136841108 / 0.13 / 0.58 / 0.00 / 0.10
rs1386754 / 141.24 / 137234214 / 1.14 / 0.60 / 0.58 / 0.26
rs728186 / 141.89 / 137969173 / 1.53 / 0.58 / 0.58 / 0.26
rs2485729 / 143.41 / 138809885 / 2.14 / 0.55 / 0.00 / 0.00
rs367697 / 144.1 / 139116025 / 2.34 / 0.55 / 0.88 / 0.21
rs1884198 / 146.34 / 139665584 / 2.83 / 0.56 / 0.0 / 0.00
rs1565843 / 146.92 / 139883213 / 2.94 / 0.57 / 0.30 / 0.04
rs4825014 / 149.06 / 140386022 / 3.25 / 0.67 / 1.71 / 0.38
rs1157574 / 150.53 / 140686340 / 3.25 / 0.67 / 0.00 / 0.00
rs17407 / 151.18 / 140910351 / 3.24 / 0.67 / 1.72 / 0.38
rs971879 / 151.93 / 141172220 / 3.24 / 0.67 / 0.30 / 0.09
rs1997686 / 154.29 / 141990887 / 3.24 / 0.67 / 1.73 / 0.38
rs1569855 / 154.73 / 142142785 / 3.24 / 0.67 / 0.00 / 0.10
rs926356 / 155.24 / 142319444 / 3.24 / 0.67 / 0.58 / 0.17
rs992566 / 155.87 / 142534400 / 3.23 / 0.67 / 0.30 / 0.09
rs2500128 / 157.06 / 142933427 / 3.23 / 0.67 / 1.79 / 0.42
rs644429 / 160.1 / 143613218 / 3.21 / 0.67 / 1.66 / 0.38
rs500004 / 161.17 / 144068644 / 3.20 / 0.66 / 0.00 / 0.10
rs2152851 / 161.65 / 144273003 / 3.20 / 0.66 / 1.73 / 0.38
rs2057209 / 162.7 / 144722069 / 3.20 / 0.66 / 1.73 / 0.38
rs871156 / 162.91 / 144813322 / 3.20 / 0.66 / 1.69 / 0.38
rs1575093 / 164.83 / 145660212 / 3.19 / 0.66 / 1.74 / 0.43
rs1336835 / 164.95 / 145747580 / 3.19 / 0.66 / 0.00 / 0.10
rs560689 / 165.77 / 146375893 / 3.20 / 0.66 / 1.73 / 0.42
rs1024694 / 166.48 / 146986102 / 3.19 / 0.66 / 1.72 / 0.38
rs1547932 / 167.3 / 147409550 / 3.19 / 0.66 / 0.30 / 0.09
rs1860929 / 168.06 / 147693062 / 3.19 / 0.66 / 0.00 / 0.10
rs764908 / 169.39 / 148185060 / 3.18 / 0.66 / 0.30 / 0.09
rs530501 / 169.74 / 148375356 / 3.18 / 0.66 / 0.88 / 0.21
rs7064676 / 170.69 / 148907051 / 3.15 / 0.64 / 0.00 / 0.00
rs480199 / 173.84 / 149423603 / 3.02 / 0.60 / 2.01 / 0.47
rs222403 / 175.99 / 149616312 / 2.96 / 0.59 / 1.44 / 0.34
rs2369604 / 179.24 / 150012708 / 2.89 / 0.57 / 0.58 / 0.04
rs644345 / 179.48 / 150087472 / 2.89 / 0.57 / 0.30 / 0.04
rs760109 / 180.17 / 150303180 / 2.89 / 0.57 / 1.69 / 0.36
rs941400* / 181.59 / 150748351 / 2.81 / 0.52 / 0.30 / 0.09
rs473491* / 190.32 / 154553040 / 2.61 / 0.35 / 0.30 / 0.09

*Denotes SNPs flanking DKC1 locus. DKC1 coordinates are 153,644,344-153,659,154 from Human Genome Build 36.3, hg18.

HUGO Name / Extended Gene Name / HUGO Name / Extended Gene Name
LOC158696 / miscRNA / MAGEA2 / melanoma antigen family A, 2
FGF13 / fibroblast growth factor 13 / CSAG2 / CSAG family, member 2
MIR504 / miRNA 504 / MAGEA12 / melanoma antigen family A, 12
SRD5A1P1 / steroid-5-alpha-reductase, alpha polypeptide 1 pseudogene 1 / CSAG1 / chondrosarcoma associated gene 1
F9 / coagulation factor IX / MAGEA3 / melanoma antigen family A, 3
MCF2 / MCF.2 cell line derived transforming sequence / CETN2 / centrin, EF-hand protein, 2
ATP11C / ATPase, class VI, type 11C / NSDHL / NAD(P) dependent steroid dehydrogenase-like
MIR505 / miRNA 505 / ZNF185 / zinc finger protein 185 (LIM domain)
CXorf66 / chromosome X open reading frame 66 / PNMA5 / paraneoplastic antigen like 5
SOX3 / SRY (sex determining region Y)-box 3 / PNMA3 / paraneoplastic antigen MA3
RP1-177G6.2 / miscRNA / LOC100287428 / similar to paraneoplastic antigen-like protein 6A
CDR1 / cerebellar degeneration-related protein 1 / PNMA6A / paraneoplastic antigen like 6A
MIR320D2 / miRNA 320D2 / MAGEA1 / melanoma antigen family A
SPANXB1 / SPANX family, member B1 / ZNF275 / zinc finger protein 275
LDOC1 / leucine zipper, down-regulated in cancer 1 / ZFP92 / zinc finger protein 92 homolog (mouse)
SPANXC / SPANX family, member C / TREX2 / three prime repair exonuclease 2
SPANXA2 / SPANX family, member A2 / HAUS7 / HAUS augmin-like complex,subunit 7
SPANXE / SPANX family, member E / BGN / biglycan
SPANXD / SPANX family, member D / ATP2B3 / ATPase, Ca++ transporting, plasma membrane 3
MAGEC3 / melanoma antigen family C, 3 / FAM58A / family with sequence similarity 58, member A
MAGEC1 / melanoma antigen family C, 1 / DUSP9 / dual specificity phosphatase 9
MAGEC2 / melanoma antigen family C, 2 / PNCK / pregnancy up-regulated non-ubiquitously expressed CaM kinase
SPANXN4 / SPANX family, member N4 / SLC6A8 / solute carrier family 6 (neurotransmitter transporter, creatine), 8
SPANXN3 / SPANX family, member N3 / BCAP31 / B-cell receptor-associated protein 31
SLITRK4 / SLIT and NTRK-like family, member 4 / ABCD1 / ATP-binding cassette, sub-family D, member 1
SPANXN2 / SPANX family, member N2 / PLXNB3 / plexin B3
UBE2NL / ubiquitin-conjugating enzyme E2N-like / SRPK3 / SRSF protein kinase
SPANXN1 / SPANX family, member N1 / IDH3G / Isocitrate dehydrogenase 3 (NAD+) gamma
SLITRK2 / SLIT and NTRK-like family, member 2 / SSR4 / signal sequence receptor, delta
CXorf1 / chromosome X open reading frame 1 / PDZD4 / PDZ domain containing 4
MIR890 / miRNA 890 / L1CAM / L1 cell adhesion molecule
MIR888 / miRNA 888 / AVPR2 / arginine vasopressin receptor 2
MIR892A / miRNA 892A / ARHGAP4 / Rho GTPase activating protein 4
MIR892B / miRNA 892B / NAA10 / N(alpha)-acetyltransferase 10, NatA catalytic subunit
MIR891B / miRNA 891B / RENBP / renin binding protein
MIR891A / miRNA891A / HCFC1 / host cell factor C1(VP16-accessory protein)
CXorf51 / chromosome X open reading frame 51 / TMEM187 / transmembrane protein 187
MIR506 / miRNA 506 / MIR3202-1 / miRNA 3202-1
MIR507 / miRNA 507 / MIR3202-2 / miRNA 3202-2
MIR508 / miRNA 508 / IRAK1 / interleukin-1 receptor-associated kinase 1
MIR514B / miRNA 514B / MIR718 / miRNA 718
MIR509-1 / miRNA 509-1 / MECP2 / methyl CpG binding protein 2 (Rett syndrome)
MIR509-2 / miRNA 509-2 / OPN1LW / opsin 1 (cone pigments), long-wave-sensitive
MIR509-3 / miRNA 509-3 / OPN1MW2 / opsin 1 (cone pigments), medium-wave-sensitive
MIR510 / miRNA 510 / OPN1MW / opsin 1 (cone pigments), medium-wave-sensitive
MIR514-1 / miRNA 514-1 / TEX28 / testis expressed 28
MIR514-2 / miRNA 514-2 / TKTL1 / transketolase-like 1
MIR514-3 / miRNA 514-3 / FLNA / filamin A, alpha
ASFMR1 / FMR1 antisense RNA / EMD / Emerin
FMR1 / fragile X mental retardation 1 / RPL10 / ribosomal protein L10
FMR1NB / fragile X mental retardation 1 neighbor / SNORA70 / H/ACA box SnoRNA 70
AFF2 / AF4/FMR2 family, member 2 / DNASE1L1 / deoxyribonuclease I-like 1
IDS / iduronate 2-sulfatase / TAZ / Tafazzin
LOC100131434 / miscRNA / ATP6AP1 / ATPase, H+ transporting, lysosomal accessory protein 1
CXorf40A / chromosome X open reading frame 40A / GDI1 / GDP dissociation inhibitor 1
MAGEA9 / melanoma antigen family A, 9 / FAM50A / family with sequence similarity 50, member A
HSFX2 / heat shock transcription factor family, X linked 2 / PLXNA3 / plexin A3
HSFX1 / heat shock transcription factor family, X linked 1 / LAGE3 / L antigen family, member 3
TMEM185A / transmembrane protein 185A / UBL4A / ubiquitin-like 4A
MAGEA11 / melanoma antigen family A, 11 / SLC10A3 / solute carrier family 10 (sodium/bile acid cotransporter family), #3
MAGEA8 / melanoma antigen family A, 8 / FAM3A / family with sequence similarity 3, member A
CXorf40B / chromosome X open reading frame 40B / G6PD / glucose-6-phosphate dehydrogenase
LOC100272228 / miscRNA / IKBKG / inhibitor of kappa light polypeptide gene enhancer in B-cells, γ
MIR2114 / miRNA 2114 / NCRNA00204B / miscRNA
MAMLD1 / mastermind-like domain containing 1 / NCRNA00204 / miscRNA
MTM1 / myotubularin 1 / CTAG1B / cancer/testis antigen 1B
MTMR1 / myotubularin related protein 1 / CTAG1A / cancer/testis antigen 1A
CD99L2 / CD99 molecule-like 2 / CTAG2 / cancer/testis antigen 2
HMGB3 / high-mobility group box 3 / GAB3 / GRB2-associated binding protein 3
MIR4330 / miRNA 4330 / DKC1** / Dyskerin
GPR50 / G protein-coupled receptor 50 / SNORA36A** / H/ACA box snoRNA 36A
VMA21 / VMA21 vacuolar H+-ATPase homolog (S. cerevisiae) / SNORA56** / H/ACA box snoRNA 56
PASD1 / PAS domain containing 1 / MPP1 / membrane protein, palmitoylated 1, 55kDa
PRRG3 / proline rich Gla (G-carboxyglutamic acid) 3 (transmembrane) / LOC100132963 / hypothetical protein LOC100132963
FATE1 / fetal and adult testis expressed 1 / F8 / coagulation factor VIII,procoagulant component
CNGA2 / cyclic nucleotide gated channel alpha 2 / H2AFB3 / H2A histone family, member B3
MAGEA4 / melanoma antigen family A, 4 / H2AFB1 / H2A histone family, member B1
GABRE / gamma-aminobutyric acid (GABA) A receptor,Ɛ / F8A1 / coagulation factor VIII-associated (intronic transcript)
MIR224 / miRNA 224 / MIR1184 / miRNA 1184
MIR452 / miRNA 452 / MIR1184-2 / miRNA 1184-2
MAGEA5 / melanoma antigen family A, 5 / FUNDC2 / FUN14 domain containing 2
MAGEA10 / melanoma antigen family A, 10 / MTCP1NB / mature T-cell proliferation 1 neighbor
GABRA3 / gamma-aminobutyric acid (GABA) A receptor,α3 / MTCP1 / mature T-cell proliferation 1
MIR105-1 / miRNA 105-1 / BRCC3 / BRCA1/BRCA2-containing complex, subunit 3
MIR767 / miRNA 767 / VBP1 / von Hippel-Lindau binding protein 1
MIR105-2 / miRNA 105-2 / RAB39B / RAB39B, member RAS oncogene family
GABRQ / gamma-aminobutyric acid (GABA) receptor, θ / CLIC2 / chloride intracellular channel 2
MAGEA6 / melanoma antigen family A, 6 / TMLHE / trimethyllysine hydroxylase, epsilon

* Names are displayed for each gene located in the linkage region between positions 136,841,108-154,553,040 (i.e. rs1539270 - rs473491) shown in Supplementary Table 4. The gene names are sequentially listed first in column 1 then in column 2. ** Genes which showed no sequence variation from reference by Sanger sequencing.