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Table 2 Rare variants unique to CDD probands

From: Neurogenetic analysis of childhood disintegrative disorder

Sex Inheritance Gene AA change Genomic coordinate (hg19) Reference Variant Brain exp PhyloPb RVIS PolyPhen2 Gene-associated OMIM disorder (#, inheritance) Variants identified in ID, ASD, EE, SCZ, DD: #, inheritance, variant type [reference]
CDD03-03
M Hemizygous NRK K336R chrX:105150568 A G Yes 5.88 n/a 0.999 (Mis3) n/a ID: 1 DN, 7 n/a missense [4244]
M Hemizygous TBC1D8B L653I chrX:106093374 C A Yes 4.84 -1.15 0.999 (Mis3) n/a ASD: 1 DN missense [23]; ID: 1 DN, 2 n/a missense [42, 43]
M Hemizygous NKRF K50R chrX:118725239 T C Yes 1.39 -0.54 0.005 (Mis1) n/a ID: 3 n/a missense [44]
M Hemizygous SAGE1 A362V chrX:134989926 C T Yes -0.03 0.01 0.000 (Mis1) n/a ASD: 1 DN missense [23]; ID: 4 n/a missense [42, 44]
CDD05-03
M Homozygous TCTEX1D2 R110C chr3:196022930 G A Yes 2.69 0.28 1.000 (Mis3) n/a SCZ: 1 DN, 20 n/a deletion [45, 46]
M Hemizygous USP26 P683L chrX:132160201 G A No -1.09 0.46 0.000 (Mis1) n/a ID: 4 n/a missense [42, 44]
CDD07-03
M De novo BBS9 L376P chr7:33376163 T C Yes 5.72 1.05 0.222 (Mis1) Bardet-Biedl syndrome 9 (615986, AR) Syndromic ID
M De novo TRRAP P1781S chr7:98548580 C T Yes 7.70 -6.14 1.000 (Mis3) n/a ASD: 3 DN missense [23]; EE: 1 DN missense [47]; SCZ: 1 DN missense, 1 DN SS [48]; DD: 3 DN missense [49]
M Homozygous DNMT3B A364T chr20:31383238 G A Yes 0.31 -1.70 0.000 (Mis1) Immunodeficiency-centromeric instability-facial anomalies syndrome 1 (242860, AR) Syndromic ID
M Hemizygous CDR1 G161R chrX:139866051 C T Yes 0.37 0.15 0.995 (Mis3) n/a ID: 2 n/a missense [42]
M Hemizygous FAM50A E136K chrX:153674872 G A Yes 6.75 -0.01 0.010 (Mis1) n/a ID: 1 n/a missense [42]; EE: 1 DN missense [47]
CDD08-03
M Hemizygous CNGA2 F385S chrX:150912129 T C No 7.56 0.49 0.999 (Mis3) n/a ID: 5 n/a missense [42, 44]
CDD09-03  
M Homozygous NOP9 A161_E162insEE chr14:24769850 * I:AGGAGG Yes 0.59 0.98 n/a n/a DD: 1 DN indel [49]
M Hemizygous ZXDA V264L chrX:57936065 C A Yes -0.44 n/a 0.000 (Mis1) n/a ID: 1 DN, 1 n/a missense [42, 43]
M Hemizygous SPANXN2 L41F chrX:142795555 C A No -1.83 0.41 0.946 (Mis2) n/a ID: 1 n/a missense [42]
CDD10-03
M De novo NAV2 R2046W chr11:20122629 C T Yes 3.78 -1.56 1.000 (Mis3) n/a ASD: 2 DN missense [23]
CDD12-03
F Homozygous ADAMTS18 S660N chr16:77359816 C T Yes 4.90 -0.09 0.001 (Mis1) Microcornea, myopic chorioretinal atrophy, and telecanthus (615458, AR)
CDD13-03 and 04 (MZ twins)a
F De novo BBS5 I76M chr2:170344335 A G Yes 1.29 0.04 0.82 (Mis2) Bardet-Biedl syndrome 5 (615983, AR) Syndromic ID
F De novo NSD1 R964W chr5:176639097 C T Yes 0.27 -1.55 0.997 (Mis3) Sotos syndrome 1 (117550, AD), Beckwith-Wiedemann syndrome (130650, AD) Syndromic ID and ASD
F De novo OGDHL 3′UTR deletion chr10:50940935-50943068 * CNV: deletion Yes 5.43 -0.54 n/a n/a  
F Hemizygous TUBGCP5 T274S chr15:22846945 A T (paternal allele deleted) Yes 8.29 -0.77 0.891 (Mis2) n/a ASD: 1 DN missense [23]; ID: 1 inh deletion [50]; EE: 1 inh deletion [50]; SCZ: 1 inh deletion [50]
CDD15-03
M De novo ZNF236 L1599H chr18:74659496 T A Yes 5.43 -1.53 0.999 (Mis3) n/a
M Hemizygous SUPT20HL2 G472R chrX:24330019 C T No 1.32 n/a 0.884 (Mis2) n/a
CDD16-03
M Homozygous PRKCSH E314_E315del chr19:11558343-11558348 * D:GGAGGA Yes 1.61 -0.89 n/a Polycystic liver disease 1 (174050, AD)  
M Hemizygous SUPT20HL2 P795A chrX:24329050 G C No -0.55 n/a 0.047 (Mis1) n/a  
M Hemizygous USP9X A843G chrX:41027363 C G Yes 7.62 -1.62 0.102 (Mis1) Mental retardation, X-linked 99 (300919, XLR and 300968, XLD) Syndromic ID and EE
M Hemizygous GATA1 A55T chrX:48649679 G A Yes 1.06 -0.60 0.993 (Mis3) Anemia (300835, XLR); Thrombocytopenia (314050, XLR and 300367, XLR)  
M Hemizygous MTMR8 N265K chrX:63564995 G T Yes 4.00 -0.77 1.000 (Mis3) n/a ASD: 1 DN missense [23], 1 hemizygous SS [51]; ID: 5 n/a missense [42, 44]
M Hemizygous DCX M51V chrX:110654052 T C Yes 0.66 -0.10 0.002 (Mis1) Lissencephaly, X-linked (300067, XL) Syndromic ID and EE
M Hemizygous CT47B1 L236P chrX:120008818 A G No -1.15 n/a 0.001 (Mis1) n/a ASD: 1 DN missense [23]; ID: 2 n/a missense [44]
CDD17-03
M Heterozygous CLUL1 5′SS disruption chr18:618107 G A (paternal) Yes 6.04 0.66 n/a n/a  
M Hemizygous BCOR F1023L chrX:39930395 G C Yes 8.97 -3.03 0.999 (Mis3) Microphthalmia, syndromic 2 (300166, XLD) Syndromic ID
M Hemizygous BEX2 Y97C chrX:102564711 T C Yes 0.78 0.64 0.046 (Mis1) n/a ASD: 1 n/a missense [52]; ID: 1 n/a missense [42]; SCZ: 1 n/a missense [52]
M Hemizygous VSIG1 Q88R chrX:107304707 A G Yes 1.19 -0.18 0.856 (Mis2) n/a ASD: 2 hemizygous SS [51]; ID: 1 n/a missense [44]
M Hemizygous SRPK3 R619Q chrX:153050929 G A Yes 7.69 -0.33 1.000 (Mis3) n/a ID: 7 n/a missense [42, 44, 53]
M Hemizygous USP9Y R122X chrY:14837084 C T Yes 2.63 n/a n/a Spermatogenic failure, Y-linked, 2 (415000, YL)  
CDD20-03a
M Homozygous KIAA2018 Q1472del chr3:113376112-113376114 * D:GCT Yes 3.58 -0.71 n/a n/a ASD: 1 DN nonsense, 4 n/a missense [22]; EE: 1 DN missense [47]; SCZ: 1 DN missense [54]
M Homozygous BRIP1 V193I chr17:59924512 C T Yes -0.69 -0.64 0.000 (Mis1) Breast cancer, early-onset (114480, AD); Fanconi anemia, complementation group J (609054, AR)  
M Hemizygous PDK3 K410Q chrX:24557261 A C Yes 2.44 0.13 0.001 (Mis1) Charcot-Marie-Tooth disease, 6 (300905, XLD)  
M Hemizygous ARSF R386Q chrX:3021857 G A Yes 6.00 0.36 0.999 (Mis3) n/a ASD: 1 n/a nonsense [51]; ID: 4 n/a missense, 3 n/a indel, 2 n/a SS [42, 44]
M Hemizygous ALAS2 V193I chrX:55047546 C T Yes 3.26 0.13 0.803 (Mis2) Anemia, sideroblastic, 1 (300751, XLR); Protoporphyria, erythropoietic (300752, XLD)  
M Hemizygous STARD8 3 bp deletion chrX:67938303-67938305 * D:AAG Yes 3.59 0.74 n/a n/a ID: 2 n/a missense, 1 n/a indel [42, 44]
M Hemizygous CXorf57 R545T chrX:105882817 G C Yes 6.24 -0.40 1.000 (Mis3) n/a ID: 2 n/a missense [42, 44]
M Hemizygous ALG13 S891F chrX:110980084 C T Yes 4.77 -1.00 0.986 (Mis3) Epileptic encephalopathy, early infantile, 36 (300884, XLD) Syndromic ID and EE
CDD21-03
F Homozygous RAD51C T287A chr17:56798128 A G Yes 5.16 0.11 0.988 (Mis3) Fanconi anemia, complementation group O (613390, AR)  
F Homozygous SHANK3 G277R chr22:51117800 G A Yes 1.95 n/a 0.002 (Mis1) Phelan-McDermid syndrome (606232, DN); Schizophrenia 15 (613950, DN) Syndromic ID, ASD, EE, SCZ
CDD22-03
M Homozygous DAP3 G5E chr1:155679584 G A Yes 1.86 -0.22 0.890 (Mis2) n/a ASD: 1 DN missense [23]
M Hemizygous ENOX2 E12K chrX:129843232 C T Yes -0.35 -0.43 0.000 (Mis1) n/a ID: 1 hemizygous, 1 n/a missense [42, 55]
  1. Abbreviations: AA amino acid, AD autosomal dominant, AR autosomal recessive, ASD autism spectrum disorder, CDD childhood disintegrative disorder, CNV copy number variant, DD developmental disorders, DN de novo, EE epilepsy/epileptic encephalopathy, F female, indel insertion/deletion, inh inherited, ID intellectual disability, M male, Mis1 Missense1 (benign), Mis2 Missense2 (possibly damaging), Mis3 Missense3 (probably damaging), MZ monozygotic, OMIM Online Mendelian Inheritance in Man, PhyloP phylogenetic P-value, PolyPhen-2 polymorphism phenotyping v2, RVIS Residual Variation Intolerance Score, SCZ schizophrenia/childhood-onset schizophrenia, SS splice site, XL X-linked, XLD X-linked dominant, XLR X-linked recessive, YL Y-linked
  2. aNo discordant variants were confirmed between monozygotic twin girls CDD13-03 and 04 (CDD) and between monozygotic twin boys CDD20-03 (CDD) and 04 (ASD)
  3. bPhyloP scores for indels and CNVs were calculated by averaging the PhyloP scores for all positions affected
  4. *wild-type sequence