Supplementary table 1. Genes selected for targeted next-generation sequencing. The HaloPlex target enrichment system allows a maximum target size of 500 kb. Our target included the 17 known CMT2 disease genes (grey). An additional 143 genes were included based on relation to other hereditary neuropathy (e.g. CMT1), functional relation to known CTM2 disease genes, such asmitochondrial dynamics, mitochondrial DNA (mtDNA) maintenance or aminoacyl-tRNA synthetases, or based on containing potential disease-causing variants in a previous CMT2 exome sequencing study.

Category / Gene Name
Associated with neuropathy / AARS / ABHD12 / ARHGEF10 / ARSA / ASAH1
ATL1 / ATP7A / BSCL2 / CANX / CCT5
CDRT4 / COX10 / CTDP1 / DCTN1 / DHH
DNAJB2 / DNM2 / DYNC1H1 / EGR2 / FAM134B
FBLN5 / FGD4 / FIG4 / GALC / GAN
GARS / GDAP1 / GJB1 / GJB3 / HARS
HK1 / HOXD10 / HSPB1 / HSPB3 / HSPB8
IFRD1 / IGHMBP2 / IKBKAP / INF2 / KARS
KIF1A / KIF1B / LITAF / LMNA / LRSAM1
MED25 / MFN2 / MPZ / MTMR2 / NDRG1
NEFH / NEFL / NGF / NINJ1 / NTRK1
PEX1 / PEX7 / PLEKHG5 / PMM2 / PMP22
PRPS1 / PRX / RAB7A / SBF2 / SCN9A
SEPT9 / SETX / SH3TC2 / SLC12A6 / SOD1
SOX10 / SPTLC1 / SPTLC2 / TDP1 / TEKT3
TRIM2 / TRPV4 / TUBB3 / WNK1
Mitochondrial dynamics / DNM1L / FIS1 / MFF / MFN1 / MTFP1
OPA1 / PHB / PHB2 / SH3GLB1 / SMCR7
SMCR7L
mtDNA maintenance / C10orf2 / DGUOK / MPV17 / POLG / POLG2
RRM2B / SUCLA2 / SUCLG1 / TK2 / TSFM
TYMP
Aminoacyl-tRNA Synthetases / AARS2 / AARSD1 / CARS / CARS2 / DARS
DARS2 / EARS2 / EPRS / FARS2 / FARSA
FARSB / HARS2 / IARS / IARS2 / LARS
LARS2 / MARS / MARS2 / NARS / NARS2
PARS2 / QARS / RARS / RARS2 / SARS
SARS2 / TARS / TARS2 / VARS / VARS2
WARS / WARS2 / YARS / YARS2
Candidate genes from previous
CMT2 exome sequencing / AHNAK / AVL9 / AXIN2 / CDRT15 / CHGB
COL5A1 / EXOSC10 / FKBP10 / FMO4 / IFT140
KANK1 / LPHN3 / MAP1B / MAP7 / MARC1
MPRIP / NCOA1 / PVRL2 / RNF157 / SLC7A5
SON / TNKS / VIT / YY1AP1 / ZNF554

Supplementary table 2. The following variants were found in the genes that were included in the HaloPlex screen either because of association with neuropathies other than CMT2, or because of functional relationship with CMT2 disease genes. For each variant, the genomic position according to the hg19 assembly is given along with the predicted amino acid change (according to SIFT Genome), gene name, the variant’s frequency in the NHLBI Exome Variant Server (EVS frequency, evs.gs.washington.edu/EVS), the variant’s frequency in the Finnish subpopulation of the 1000Genomes project (1000Genomes.org), and finally the number of patients in our cohort in whom the variant was found. The corresponding RefSeq sequences and base changes are also indicated.

Variant / AA Change / Gene
(RefSeq) / EVS frequency / 1000Genomes frequency in Finnish samples / No. of Samples
11,3050233, C/T
(c.775G>A) / p.(Gly259Ser) / CARS
(NM_139273.3) / 0.0058 / 0.022 / 2
9,95036742, G/A
(c.956C>T) / p.(Thr319Ile) / IARS
(NM_002161.5) / <0.0001 / 0.011 / 1
14,105179616, C/T
(c.2848C>T) / p.(Arg950Trp) / INF2
(NM_022489.3) / 0.0004 / - / 1
16,75665388, C/T
(c.1262G>A) / p.(Arg393Glu) / KARS
(NM_001130089.1) / 0.0014 / - / 1
2,228197164, C/T
(c.289C>T) / p.(Pro71Ser) / MFF
(NM_001277062.1) / 0.0002 / - / 1
12,7079391, C/G
(c.180G>C) / p.(Gln60His) / PHB2
(NM_001144831.1) / - / - / 1
6,88239320, C/G
(c.818G>C) / p.(Arg273Pro) / RARS2
(NM_020320.3) / 0.0007 / 0.011 / 1
2,167160752, G/C
(c.684C>G) / p.(Ile228Met) / SCN9A
(NM_002977.3) / 0.0012 / 0.011 / 1
5,33457501, T/C
(c.977T>C) / p.(Ile326Thr) / TARS
(NM_001258437.1) / 0.0024 / 0.011 / 1
16,66583871, G/A
(c.94C>T) / p.(Arg32Trp) / TK2
(NM_004614.4) / - / - / 2

Supplementary table 3. This table lists the oligonucleotide sequences of primers used in this study.

Gene / Exon / Forward Primer / Reverse Primer
KIF1B / 10 / GACTGATTTGCCTTTCTTGGGA / CTCCAAAACAGACACAGGACA
KIF1B / 16 / AGAAGCCTGGCCTCTTGTAG / TTTCAACCCCTTCCCTTTAGTT
KIF1B / 42 / ACGTGGTCAGCTATCCCAAG / GGCTGCTGTGGAGAAATCAG
TRPV4 / 13 / TGAGAATGACACCCTCCACC / GAGGGTGGCTGGTAGAGTG
GARS / 1 / TACGCGGCGATTTCATCATG / GATGACCAGAAGAAGGCCCT
GARS / 4 / GGGAGTATAGGTATCAGTTTCTCATGT / TTTATTTAAAGTAGGATACCCCCACTC
GARS / 5 / TGGATATAAATATTGATGGGGAAT / TTTAATGAAAGACATCTGAGAGAAAG
GARS / 7 / TGCCTTGTTTTCTCTGTCTTTT / TTTTCCTTCATAACATTGATATTTACC
GARS / 10 / CCGATATCTTGGCTTTGAAGA / AAGTGCACAAAAATTCATTTGG
LRSAM1 / 7 / CACAGGGGTCTTTCTTCTGC / TGAGTGACTGCCTGGTCTCA
AARS / 21 / TCCCTCAATCCCATCTTCTG / ACTGCTCCCAAGTGTGTTCC
DNM2 / 7 / CATGCCACCCTTTCTGATCT / CCCTGTGGCTGATGGAAG
LMNA / 16 / CTACACCTGGCTGAGGTTCC / TAGCGTTTGCCAAAACCACT
DYNC1H1 / 25 / TCTCACATTTTTGCATACCTCA / GATTGGTCTGCGTTTTCACC
DYNC1H1 / 30 / TTAACGCTATCATCTCATTCTCAG / AACATGATTATGAAGAATTCTAGGC
DYNC1H1 / 48 / ACATGGGCCTCTTTCTCAG / TCTGTTGATCTCAAAACTGAACC