Table S1: List of the 646 known pathogenic genes targeted in the present study and their associated mode of inheritance. ARID: autosomal-recessive

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Milton Rodgers
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1 Table S1: List of the 646 known pathogenic genes targeted in the present study and their associated mode of inheritance. : autosomal-recessive intellectual disability; : autosomal-dominant intellectual disability; : X-linked intellectual disability. ABAT ABCD1 ABRA ACBD6 ACSL4 ACTB ACTG1 ACY1 ADAR ADAT3 ADD3 ADK ADRA2B ADSL AGAP1 AHI1 AIMP1 AIPL1 AKT3 ALDH7A1 ALG1 ALG11 ALG12 ALG13 ALG2 ALG3 ALG6 ALG8 ALG9 AMPD2 AMT ANK3 ANKRD11 AP1S2 AP3B1 AP4B1 AP4E1 AP4M1 AP4S1 ARFGEF2 ARHGEF6 ARHGEF9 1A 1B ARL13B ARL6 ARNT2 ARSA ARX ASCL1 ASNS ASPA ASPM ASXL1 ASXL3 ATM ATP5A1 ATP6AP2 ATP6V0A2 ATP7A ATP8A2 ATR ATRX ATXN1 B3GALNT2 B3GALTL B3GNT1 B4GALT1 B9D1 B9D2 BBIP1 BBS1 BBS10 BBS12 BBS2 BBS4 BBS5 BBS7 BBS9 BCAP31 BCOR BLM BOLA3 BRAF BRD2 BRD3 BRWD3 BSCL2 BUB1B C11orf46 C12orf57 C2ORF86 C3orf58 C5orf42 C8orf41 C9orf86 CA8 CACNA1G CACNG2 CAPN10 CASC5 CASK CASP2 CBL CBS CC2D1A CC2D2A CCDC22 CCDC28B CCDC88C CCNA2 CDC6 CDH15 CDK19 CDK5RAP2 CDK6 CDKL5 CDKN1C CDT1 CECR2 CELF4 CENPJ CEP135 CEP152 CEP290 CEP41 CEP63 CEP89 CHD2 CHD7 CHMP1A CHN1 CLCN4 CLIC2 CLIP2 CLN3 CLN5 CLN6 CLN8 CNKSR1 CNKSR2 CNTN2 CNTN4 CNTNAP2 COASY COG1 COG4

2 COG5 COG6 COG7 COG8 COQ5 COX7B CRADD CRBN CREBBP CSPP1 CTCF CTNNB1 CTSD CUL4B DAG1 DARS DCHS1 DCX DDOST DDX11 DEAF1 DHCR24 DHCR7 DLG3 DLK1 DNM2 DNMT1 DNMT3A DNMT3B DOCK8 DOLK DPAGT1 DPM1 DPM2 DPM3 DYNC1H1 DYRK1A EBP EEF1B2 EFTUD2 EHMT1 EIF2B1 EIF2B2 EIF2B3 EIF2B4 EIF2B5 EIF2S3 EIF4A3 ELF2 ELOVL4 ELP2 ENOSF1 ENTPD1 EP300 EPB41L1 ERCC1 ERCC4 ERLIN2 ESCO2 EVC2 EXOC4 EXOSC3 EYA1 EZH2 FAM126A FAM58A FANCB FASN FAT4 FBXL4 FGD1 FIG4 FKRP FKTN FLNA FMN2 FMR1 FOLR1 FOXG1 FOXP1 FOXP2 FRY FTSJ1 GAD1 GALC GAMT GATAD2B GATM GCSH GDI1 GFAP GJC2 GK GLDC GLI3 GLIPR1 GMPPA GNAO1 GON4L GPC3 GPD2 GPR56 GRIA3 GRID2 GRIK2 GRIN1 GRIN2A GRIN2B GTF2I HCCS HCFC1 HDAC4 HDAC8 HEPACAM HERC2 HESX1 HEXA HIP1 HIST1H4B HIST3H3 HOXA1 HPRT1 HRAS HSD17B10 HSPD1 HUWE1 IDS IER3IP1 IGBP1 IGF1R IKBKG IL1RAPL1 INO80 INPP4A INPP5E IQSEC2 ISPD JAG1 J2 JHDM1D JMJD1C KANK1 KANSL1 KAT6A KAT6B KCNJ10 KCNK9 KCNQ2 KCNT1 KCTD13 KDM5A KDM5C KDM6A KDM6B KIAA0196 KIAA1279 KIAA2022 KIF11 KIF1A

3 KIF2A KIF5C KIF7 KIRREL3 KLF8 KLHL15 KDM2A KMT2C KMT2D KPTN KRAS L1CAM L2HGDH LAMA1 LAMC1 LAMP2 LARGE LARP7 LAS1L LIAS LIG4 LIMS1 LINS LRP2 LYRM7 MACROD2 MAGEL2 MAN1B1 MAOA MAOB MAP2K1 MAP2K2 MBD5 MBTPS2 MCPH1 MECP2 MED12 MED13L MED17 MED23 MEF2C MFSD8 MGAT2 MID1 MID2 MKKS MKL1 MKL2 MKS1 MKS1 MLC1 MOGS MPDU1 MPDZ MPI MTHFR MTOR MTR MYCN MYOCD NAA10 NAGLU NALCN NDE1 NDP NDST1 NDUFA1 NFIX NHS NID1 NIN NIPBL NLGN3 NLGN4X NLRP2 NLRP7 NPHP1 NR1I3 NRAS NRXN1 NSD1 NSDHL NSUN2 OCLN OCRL OFD1 OPHN1 ORC1 ORC4 ORC6 OSTM1 OTC PACS1 PAFAH1B1 PAK3 PARP1 PCDH19 PCNT PDE4D PDE6D PDHA1 PDHX PECR PEX1 PEX10 PEX12 PEX13 PEX14 PEX16 PEX19 PEX2 PEX26 PEX3 PEX5 PEX6 PEX7 PGAP2 PGAP3 PGK1 PGM1 PHC1 PHF21A PHF6 PHF8 PIGA PIGN PIGW PIK3CA PIK3R2 PLCB1 PLP1 PMM2 PNKP PNPO PNPT1 POLG POLR3B POMGnT1 POMK POMT1 POMT2 PORCN PPT1 PQBP1 PRKCG PRKRA PRMT10 PRMT7 PRPS1 PRRT2 PRSS12 PSAP PTCH1 PTCHD1 PTEN PTPN11 PUF60 RAB18 RAB36

4 RAB39B RAB3GAP1 RAB3GAP2 RAD21 RAI1 RALGDS RANBP2 RARS2 RBBP8 RBM10 RELN RFT1 RGS7 RIT1 RMND1 RNASEH2A RNASEH2B RNASEH2C RNF168 RPGRIP1L RPL10 RPS6KA3 RTTN SALL1 SALL4 SAMHD1 SATB2 SCAPER SCLT1 SCN1A SCN2A SCN8A SCRIB SEMA3E SEPSECS SERPINA7 SETBP1 SETD2 SETD5 SETMAR SGK196 SHANK3 SHH SHOC2 SHROOM4 SIK1 SIM2 SIX3 SIX5 SKI SLC12A2 SLC16A2 SLC19A3 SLC25A19 SLC25A22 SLC25A5 SLC2A1 SLC31A1 SLC33A1 SLC35A1 SLC35A2 SLC35A3 SLC35C1 SLC4A4 SLC6A8 SLC9A6 SLITRK1 SMARCA2 SMARCA4 SMARCB1 SMARCE1 SMC1A SMC3 SMS SNAP29 SNX27 SOS1 SOX10 SOX2 SOX3 SOX5 SOX9 SPTAN1 SRCAP SRD5A3 SRF SRPX2 SSR4 ST3GAL3 ST3GAL5 STAG2 STAMBP STIL STT3A STT3B STXBP1 SUMF1 SURF1 SYN1 SYNGAP1 SYP SZT2 TAF1 TAF2 TAF6 TBC1D20 TBC1D24 TBC1D32 TBC1D7 TBX1 TCF4 TCTN1 TCTN2 TCTN3 TECR TH THOC2 THOC6 TIMM8A TM4SF20 TMCO1 TMEM135 TMEM138 TMEM165 TMEM216 TMEM231 TMEM237 TMEM5 TMEM67 TMPRSS4 TNK2 TRAPPC9 TREX1 TRIM32 TRIM32 TRIO TRMT1 TRMT10A TSC1 TSC2 TSEN2 TSEN34 TSEN54 TSPAN7 TTC21B TTC8 TTI2 TUBA1A TUBA8 TUBB2B TUBB3 TUBB4A TUBG1 TUBGCP6 TUSC3 TWIST1 UBE2A UBE3A UBR7

5 UPF3B VLDLR VPS13B VRK1 WAC WDR45 WDR45L WDR62 WDR81 WWOX XYLT1 ZBTB18 ZBTB20 ZBTB40 ZC3H14 ZC4H2 ZCCHC8 ZDHHC15 ZDHHC9 ZEB2 ZIC2 ZNF335 ZNF423 ZNF526 ZNF711.

6 Table S2: List of the 610 candidate genes targeted in the present study. AGO1 ACTL6A ACTL6B ADNP2 ADRB2 AEBP2 ALKBH8 AMIGO2 ANKRA2 ANKRD12 APBA1 APBB1 APPL1 APPL2 ARHGAP15 ARHGAP32 2 3B 4B ARIH1 ARL6 ARRB1 ASCC3 ASF1A ASF1B ASH1L ASH2L ASTN2 ASZ1 ATF2 ATF7IP ATXN7L3 AURKA AURKB AVPR1A BABAM1 BANP BAZ1A BAZ1B BAZ2A BAZ2B BCORL1 BDNF BHLHE41 BHMT BMI1 BMP4 BPTF BRD1 BRD4 BRD7 BRD8 BRE BRPF1 BRPF3 BRWD1 BTG1 BTG2 BZRAP1 C11ORF30 C14ORF169 C17ORF49 C2ORF86 CA6 CABIN1 CACNA1D CACNA1F CACNA1H CADM1 CADPS2 CAMK2G CAMTA2 CARM1 CBX1 CBX2 CBX4 CBX5 CBX6 CBX7 CBX8 CCDC101 CCDC28B CDH10 CDH11 CDH18 CDH2 CDH6 CDH9 CDYL CDYL2 CEBPB CHD1 CHD3 CHD4 CHD5 CHD6 CHD8 CHD9 CHL1 CHMP1B CIR1 CLOCK CNR1 CRABP1 CREB1 CSMD1 CSNK2A1 CSRP2BP CTCFL CTNND2 CTR9 CTXN1 CUX2 CXORF36 CXXC1 DAB1 DAPK1 DAPK3 DBX2 DCDC2 DDX17 DEK DGAT2 DGCR8 DISC1 DLG1 DLG2 DLG4 DLX1 DLX2 DMAP1 DNAJC2 DNER DNM3 DNMT3L DOT1L DPF3 DPP10 DPP6 DPY30 DR1 DRD1 DRD2 DRD3 DRD4 DSCAM EDF1 EED EEF2K EFEMP1 EGR1 EHMT2 EID1 ELP3 EMID2 EN2 ENY2 EP400 EPC1 EPC2 EPHA7 ERBB4 ESCO1 ETF1 EXOC6B EYA2 EYA3 EZH1 FAAH2 FAM175A FAM48A FAM65A FAT1 FBXO11 FBXO40 FHIT FLYWCH2 FOS FOXA2 FOXA3 FTSJ2 FTSJ3 FTSJD2 GABRA4 GABRB1 GABRB3 GABRD GALNT13 GATAD2A GFI1B GMNN GPC1 GPR6 GRIA2 GRID2 GRIK1 GRM3 GRM5 GRM7 GRM8 GRPR GRTP1 GSK3A GSPT1 GTF2IRD1 GTF3C4 H2AFY H2AFY2 HAT1 HDAC1 HDAC10 HDAC11 HDAC2 HDAC3 HDAC5 HDAC6 HDAC7 HDAC9 HENMT1 HES1 HEY2 HIC1 HIF1A HINFP HIRA HIVEP2 HLTF HMG20A HMG20B HMGN2 HMGN3 HNRNPU HOXB2 HS3ST1 HS6ST2 HTR1B HTR2A HTR3A HTR3C HTR7 ICMT ID1 IKZF1 ING2 ING3 ING4 ING5 ISL1 ITGAX ITGB1 KDM8 JMJD6 KANSL2 KANSL3 KAT2A KAT2B KAT5 KAT7 KAT8 KDM1A

7 KDM1B KDM2B KDM3A KDM3B KDM4A KDM4B KDM4C KDM4D KDM4DL KDM5B KPNA2 L3MBTL L3MBTL2 L3MBTL3 L3MBTL4 LARP6 LCMT1 LEO1 LIN7A LIX1 LMX1A LRFN5 LRWD1 LYNX1 MAEL MAGEA1 MAGEA2B MAP2 MAP2K3 MAP3K7 MAPK10 MAPK8 MAPRE3 MARCKS MARK1 MBD1 MBD2 MBD3 MBD4 MBD6 MBTD1 MCRS1 MDGA2 MEAF6 MECOM MED13 MED24 MEF2B MEF2D METTL11A METTL14 METTL3 MGEA5 MGLL MKRN3 MLH1 KMT2C MLL5 MORF4L1 MORF4L2 MPHOSPH8 MRGBP MSH2 MSL1 MSL2 MSL3 MTA1 MTA2 MTF1 MYB MYSM1 MYT1 NAA60 NAB2 NAV2 NCAM2 NCOA1 NCOA2 NCOA6 NCOR1 NCOR2 NDN NDNL2 NEFH NEK6 NELL2 NENF NGF NKAIN2 NKX3-1 NLGN1 NNAT NOTCH1 NPAS2 NPTX1 NR2C1 NR2E1 NRCAM NRG1 NRG4 NRIP1 NRP1 NRP2 NTAN1 NTF3 NTM NTN1 NTN4 NTNG1 NTRK1 NTRK2 NTRK3 NUDT21 OGT OLIG1 OPRM1 OXTR PADI4 PAF1 PAK1 PAX5 PAXIP1 PBRM1 PCDH10 PCDH11X PCDH8 PCDH9 PCGF1 PCNA PER1 PHB PHF1 PHF13 PHF15 PHF16 PHF17 PHF20 PICK1 PITX1 PKN1 PKN2 PLD6 POLE3 POLE4 PON1 PPARGC1B PRDM1 PRDM6 PRDM9 PRKAA1 PRKAA2 PRKCB PRKG2 PRMT2 PRMT3 PRMT5 PRMT6 PRMT8 PTF1A PTPRN2 PTPRT PYGO2 RAB3A RAB3B RAB3D RAB6A RAPGEF4 RASGEF1B RB1CC1 RBBP4 RBBP5 RBBP7 RBFOX1 RBL1 RBL2 RCBTB1 RCOR1 RERE REST RFWD2 RFX4 RGS6 RHOF RIMS3 RING1 RNF2 RNF20 RNF40 RNF8 ROBO1 RORB RPS6KA5 RSF1 RUVBL1 RUVBL2 RYBP SALL2 SALL3 SAP130 SAP18 SAP30 SATB1 SCRIB SDC3 SEMA4C SEMA5A SEMA6B SERPINI1 SETD1A SETD1B SETD3 SETD4 SETD6 SETD7 SETD8 SETDB1 SETDB2 SEZ6L2 SF3B1 SH3BGRL2 SHANK2 SIM1 SIN3A SIN3B SIRT1 SIRT2 SIRT6 SKP1 SLC25A12 SLC4A10 SLC6A1 SLC6A3 SLC6A4 SLC9A9 SLITRK2 SLITRK4 SMARCA5 SMARCAD1 SMARCC1 SMARCC2 SMARCD1 SMARCD2 SMARCD3 SMYD2 SMYD3 SP1 SP2 SP5 SPEN SPOCK1 SRFBP1 SS18L1 STAG1 STK24 STMN2 STX1A SUDS3 SUPT16H SUPT3H SUPT7L SUV39H1 SUV39H2 SUV420H1 SUV420H2 SUZ12 SYCP1 SYN2 SYNCRIP SYT1 TADA1 TADA2A TADA2B TAF10 TAF12 TAF1L

8 TAF4 TAF5 TAF5L TAF6L TAF7 TAL1 TBL1X TBL1XR1 TCF21 TDRD1 TDRD3 TDRD5 TDRD9 TET1 TFAP4 THBD TLE3 TLK1 TLK2 TMEM195 TMEM66 TMOD2 TNFRSF19 TOP2A TOP2B TOPBP1 TRAF6 TRIM45 TRMT112 TRPC5 TRRAP TSPYL2 UBAC2 UBAP2L UBE2B UBE2E1 UBE2H UBE2N UBN1 UBR2 UHRF1BP1 UNC5A USF1 USP16 USP21 USP22 USP3 UTP3 VPS72 VSNL1 WDR13 WDR5 WDR7 WDR8 WDR82 WHSC1 WHSC1L1 NELFA WSB1 YEATS2 YEATS4 YWHAB YWHAE YWHAH YY1 ZBTB7A ZDHHC14 ZFHX4 ZMYM3 ZMYND15 ZMYND8 ZNF217 ZNF347 ZNF385B ZNF721 ZNF804A

9 Table S3: Selection of variants of unknown or probably benign significance. See the text for further commentaries. Patient Gene Genomic position (hg19) transcript coding Protein Inheritance 6 ASCC3 chr6: NM_ c.1464dupc p.tyr489leufster5 de novo 12 CACNA1H chr16: NM_ c.2389c>t p.arg797cys de novo 37 CTCFL chr20: NM_ c.394c>t p.gln132ter de novo 38 HUWE1 chrx: NM_ c.344c>t p.ser115phe de novo 39 PDE4D chr5: NM_ c.65+2t>a splicing? de novo 40 C22orf39 chr22: NM_ c.244t>c p.trp82arg de novo 41 NLGN4X chrx: NM_ c.1361_1372del12 p.val454_ala457del de novo 42 BCOR chrx: NM_ c.4981c>t p.arg1661ter maternal (X-linked) 43 SHROOM4 chrx: NM_ c.2512_2514delcat p.his838del maternal (X-linked) 44 MECP2 chrx: NM_ c.1164_1172del9 + c.1191_1202del12 + c.1219_1227del9 p.lys389_pro391del+ Leu398_Pro401del + Ser407_Glu409del maternal (X-linked)

10 Table S4: Main clinical characteristics of the patients with pathogenic or probably pathogenic variants, as well as some variants of unknown clinical consequence. Patient DECIPHER ID Chr. sex Gene HGVS code Genotype Phenotype XY MED12 chrx:g g>a Hemizygous XX NFIX chr19:g ct>c Heterozygous XX CASK chrx:g a>c Heterozygous XX NIPBL chr5:g caat>c Heterozygous Abnormality of the genitourinary system, Blepharophimosis, Brachycephaly, Depressed nasal bridge, Growth delay, Hypertonia, Intellectual disability, Microcephaly, Microretrognathia, Muscular hypotonia, Postnatal growth retardation Abnormality of the fontanelles or cranial sutures, Abnormality of the hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the palate, Abnormality of the philtrum, Abnormality of the teeth, Decreased body weight, Downslanted palpebral fissures, Feeding difficulties, Feeding difficulties in infancy, Hearing impairment, Intellectual disability, Intrauterine growth retardation, Motor delay, Muscular hypotonia, Neonatal hypotonia, Pierre-Robin sequence, Prominent forehead, Short stature Abnormality of the nose, Aggressive behavior, Delayed speech and language development, Hypertelorism, Hypertonia, Intellectual disability, Intrauterine growth retardation, Low-set ears, Microcephaly, Micrognathia, Motor delay, Muscular hypotonia, Stereotypic behavior Abnormality of the hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the philtrum, Abnormality of the skeletal system, Abnormality of the teeth, Delayed speech and language development, Facial asymmetry, Hyperactivity, Hypertelorism, Intellectual disability, Intrauterine growth retardation, Macrotia, Low-set ears, Microcephaly, Synophrys, Upslanted palpebral fissure

11 XY KMT2D chr12:g ga>g Heterozygous XY RPS6KA3 chrx:g t>a Hemizygous XY SLC16A2 chrx:g c>t Hemizygous XY UBE3A chr15:g c>t Heterozygous XY NSDHL chrx:g g>a Hemizygous hair, Abnormality of the mouth, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Abnormality of the skeletal system, Anteverted ears, Autistic behavior, Decreased body weight, Delayed speech and language development, Feeding difficulties, Hearing impairment, Intellectual disability, Macrotia, Low-set ears, Mandibular prognathia, Microcephaly, Motor delay, Muscular hypotonia, Short stature, Stereotypic behavior Abnormality of the male genitalia, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Abnormality of the skeletal system, Abnormality of the teeth, Aggressive behavior, Anteverted ears, Decreased body weight, Delayed closure of the anterior fontanelle, Delayed speech and language development, Epicanthus, Hypermetropia, Hypertelorism, Hypertrichosis, Intellectual disability, Intrauterine growth retardation, Macrotia, Long eyebrows, Low anterior hairline, Low-set ears, Motor delay, Muscular hypotonia, Neonatal hypotonia, Pierre-Robin sequence, Short palm, Short stature, Sleep disturbance, Tapered finger, Thick vermilion border Abnormality of the hand, Abnormality of the head, Abnormality of the mouth, Abnormality of the palate, Autistic behavior, Delayed speech and language development, Epicanthus, Hypertelorism, Intellectual disability, Motor delay, Muscular hypotonia, Neonatal hypotonia, Nystagmus, Sleep disturbance Gait disturbance, Happy demeanor, Intellectual disability, Microcephaly, Poor speech Severe intellectual disability, Seizures, Spasticity, Atrophy of optic discs, Microcephaly, Plagiocephaly, Skeletal abnormalities, High nasal bridge, Strabismus, Micrognathia

12 XY TAF1 chrx:g g>c Hemizygous XX SMC3 chr10:g g>a Heterozygous XX DYRK1A chr21:g acagat>a Heterozygous XY SETBP1 chr18:g t>c Heterozygous XX PTPN11 chr12:g a>g Heterozygous hair, Abnormality of the male genitalia, Abnormality of the skeletal system, Decreased body weight, Intrauterine growth retardation, Low-set ears, Microcephaly, Motor delay, Pierre- Robin sequence, Strabismus hair, Abnormality of the hand, Abnormality of the nose, Abnormality of the palate, Abnormality of the skeletal system, Facial asymmetry, Feeding difficulties, Hearing impairment, Hypertrichosis, Intellectual disability, Intrauterine growth retardation, Long eyebrows, Low-set ears, Microcephaly, Neonatal hypotonia, Synophrys hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Abnormality of the teeth, Delayed speech and language development, Downslanted palpebral fissures, Hypertelorism, Intellectual disability, Low-set ears, Microcephaly, Micrognathia, Motor delay, Short stature, Stereotypic behavior, Symptomatic seizures hand, Abnormality of the male genitalia, Abnormality of the mouth, Abnormality of the philtrum, Abnormality of the skeletal system, Decreased body weight, Feeding difficulties in infancy, Hearing impairment, Hypertonia, Intellectual disability, Low-set ears, Microcephaly, Micrognathia, Motor delay, Muscular hypotonia, Short stature, Symptomatic seizures hair, Abnormality of the nose, Decreased body weight, Downslanted palpebral fissures, Hypertelorism, Intellectual disability, Intrauterine growth retardation, Macrotia, Low-set ears, Macrocephaly, Motor delay, Muscular hypotonia,

13 Prominent forehead, Short stature, Symptomatic seizures XY KMT2A chr11:g t>ta Heterozygous XY MED13L chr12:g c>t Heterozygous XY MED13L chr12:g g>a Heterozygous hand, Abnormality of the male genitalia, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Aggressive behavior, Decreased body weight, Delayed speech and language development, Downslanted palpebral fissures, Feeding difficulties, Hypertelorism, Hypertrichosis, Intellectual disability, Low-set ears, Microcephaly, Motor delay, Muscular hypotonia, Neonatal hypotonia, Pierre-Robin sequence, Posteriorly rotated ears, Short stature, Telecanthus Aggressive behavior, Autism spectrum disorder, Decreased body weight, Depressed nasal bridge, Downslanted palpebral fissures, Hearing impairment, Intellectual disability, Low-set ears, Muscular hypotonia Dental crowding, Depressed nasal bridge, Downslanted palpebral fissures, Intellectual disability, Low-set ears, Moderately short stature, Muscular hypotonia, Prominent forehead, Unilateral renal agenesis XY KDM6A chrx:g tcagatga CGG>T Hemizygous Abnormality of the mouth, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Anteverted ears, Decreased body weight, Delayed speech and language development, Epicanthus, Hyperactivity, Intellectual disability, Low-set ears, Microcephaly, Motor delay, Myopia, Short stature, Strabismus XX ZBTB20 chr3:g c>g Heterozygous Abnormality of the hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the philtrum, Abnormality of the skeletal system, Abnormality of the teeth, Agenesis of corpus callosum, Aggressive behavior, Anteverted ears, Autistic behavior, Delayed speech and language development, Downslanted palpebral fissures, Epicanthus,

14 Feeding difficulties, Hypertelorism, Hypertrichosis, Intellectual disability, Macrocephaly, Motor delay, Muscular hypotonia, Prominent forehead, Sleep disturbance, Strabismus XX NDST1 chr5:g g>a Homozygous XX KCNT1 chr9:g g>a Heterozygous XX 1B chr6:g c>t Heterozygous XX KMT2D chr12:g gt>g Heterozygous Abnormality of the mouth, Abnormality of the nose, Abnormality of the skeletal system, Aggressive behavior, Anteverted ears, Decreased body weight, Delayed speech and language development, Developmental regression, Hyperactivity, Hypertelorism, Hypertonia, Intellectual disability, Motor delay, Muscular hypotonia, Stereotypic behavior, Symptomatic seizures Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the philtrum, Abnormality of the teeth, Delayed speech and language development, Hypertrichosis, Intellectual disability, Microcephaly, Motor delay, Muscular hypotonia, Sleep disturbance, Stereotypic behavior, Strabismus, Symptomatic seizures Abnormality of the hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the palate, Abnormality of the philtrum, Abnormality of the teeth, Decreased body weight, Delayed speech and language development, Feeding difficulties, Feeding difficulties in infancy, Hypertelorism, Hypertrichosis, Intellectual disability, Intrauterine growth retardation, Micrognathia, Motor delay, Muscular hypotonia, Myopia, Neonatal hypotonia, Short stature, Upslanted palpebral fissure hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the palate, Abnormality of the skeletal system, Abnormality of the teeth, Autistic behavior, Facial asymmetry, Hearing impairment, Hypertrichosis, Intellectual disability, Macrotia, Low-set ears, Microcephaly, Motor delay, Muscular hypotonia, Stereotypic behavior

15 XY ANKRD11 chr16:g cctca>c Heterozygous XY RAD21 chr8:g c>t Heterozygous XX KMT2A chr11:g tc>t Heterozygous Abnormality of the hair, Abnormality of the hand, Abnormality of the male genitalia, Abnormality of the mouth, Abnormality of the nose, Abnormality of the philtrum, Abnormality of the skeletal system, Abnormality of the teeth, Anteverted ears, Autistic behavior, Delayed speech and language development, Facial asymmetry, Feeding difficulties, Hyperactivity, Hypertelorism, Intellectual disability, Intrauterine growth retardation, Long eyebrows, Low-set ears, Macrocephaly, Motor delay, Muscular hypotonia, Neonatal hypotonia, Prominent forehead, Stereotypic behavior, Synophrys, Upslanted palpebral fissure Abnormality of the hand, Abnormality of the male genitalia, Abnormality of the philtrum, Anteverted ears, Decreased body weight, Delayed speech and language development, Intellectual disability, Intrauterine growth retardation, Macrotia, Long eyebrows, Low-set ears, Microcephaly, Myopia Abnormality of the hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Aggressive behavior, Delayed speech and language development, Epicanthus, Hypertelorism, Hypertrichosis, Intellectual disability, Intrauterine growth retardation, Macrotia, Microcephaly, Posteriorly rotated ears, Short stature, Strabismus, Synophrys XY PIGN chr18:g g>a + chr18:g at>a Heterozygous Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the teeth, Anteverted ears, Delayed speech and language development, Epicanthus, Increased body weight, Intellectual disability, Motor delay, Muscular hypotonia, Neonatal hypotonia, Stereotypic behavior, Symptomatic seizures, Tall stature XY KMT2D chr12:g g>a Heterozygous fontanelles or cranial sutures, Abnormality of the hand, Abnormality of the nose, Abnormality of the palate, Decreased body weight, Feeding difficulties, Intellectual disability,

16 Intrauterine growth retardation, Micrognathia, Motor delay, Muscular hypotonia, Neonatal hypotonia, Short stature, Upslanted palpebral fissure XX 1A chr1:g a>t Heterozygous XY AGO1 chr1:g g>a Heterozygous XY J2 chr6:g c>t Heterozygous XY SIN3B chr19:g ca>c Heterozygous hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the palate, Agenesis of corpus callosum, Aggressive behavior, Decreased body weight, Delayed speech and language development, Facial asymmetry, Feeding difficulties, Hypertonia, Hypertrichosis, Intellectual disability, Macrotia, Long eyebrows, Motor delay, Muscular hypotonia, Pierre-Robin sequence, Short stature, Strabismus, Symptomatic seizures Abnormality of the kidney, Abnormality of the mouth, Abnormality of the nose, Autistic behavior, Delayed speech and language development, Epicanthus, Hyperactivity, Increased body weight, Intellectual disability, Macrotia, Motor delay, Muscular hypotonia, Sleep disturbance, Stereotypic behavior, Tall stature Abnormality of the hand, Abnormality of the nose, Autistic behavior, Blindness, Delayed speech and language development, Downslanted palpebral fissures, Increased body weight, Intellectual disability, Motor delay, Muscular hypotonia, Stereotypic behavior, Strabismus, Synophrys Abnormality of the hair, Abnormality of the nose, Aggressive behavior, Autistic behavior, Delayed speech and language development, Hearing impairment, Increased body weight, Intellectual disability, Macrocephaly, Motor delay, Muscular hypotonia, Neonatal hypotonia, Prominent forehead, Stereotypic behavio

17 XY FBXO11 chr2:g cat>c Heterozygous XY MAP3K7 chr6:g g>a Heterozygous XX HDAC2 chr6:g c>t Heterozygous XX SMARCC2 chr12:g g>c Heterozygous XX CTCFL chr20:g g>a Heterozygous XX HUWE1 chrx:g g>a Heterozygous Abnormality of the hand, Abnormality of the kidney, Abnormality of the philtrum, Abnormality of the skeletal system, Anteverted ears, Autistic behavior, Decreased body weight, Delayed speech and language development, Epicanthus, Intrauterine growth retardation, Microcephaly, Motor delay, Stereotypic behavior, Strabismus Abnormality of the male genitalia, Abnormality of the nose, Abnormality of the philtrum, Abnormality of the skeletal system, Hypertelorism, Intellectual disability, Intrauterine growth retardation, Micrognathia Autistic behavior, Delayed speech and language development, Developmental regression, Hyperactivity, Intellectual disability, Muscular hypotonia, Stereotypic behavior, Symptomatic seizures Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the skeletal system, Decreased body weight, Delayed speech and language development, Hypertrichosis, Intellectual disability, Intrauterine growth retardation, Microcephaly, Motor delay, Muscular hypotonia, Short stature, Sleep disturbance, Symptomatic seizures, Synophrys hand, Abnormality of the kidney, Abnormality of the teeth, Delayed speech and language development, Downslanted palpebral fissures, Feeding difficulties, Hearing impairment, Intellectual disability, Intrauterine growth retardation, Macrotia, Low-set ears, Micrognathia, Motor delay, Muscular hypotonia, Neonatal hypotonia Abnormality of the mouth, Abnormality of the nose, Autistic behavior, Decreased body weight, Delayed speech and language development, Hypertelorism, Hypertonia, Intellectual disability, Intrauterine growth retardation, Macrotia, Low-set

18 ears, Motor delay, Short stature, Stereotypic behavior, Symptomatic seizures, Upslanted palpebral fissure XY PDE4D chr5:g a>t Heterozygous XY C22orf39 chr22:g a>g Heterozygous Abnormality of the mouth, Abnormality of the philtrum, Abnormality of the teeth, Aggressive behavior, Delayed speech and language development, Hyperactivity, Hypermetropia, Hypertelorism, Intellectual disability, Low-set ears, Motor delay, Muscular hypotonia, Stereotypic behavior, Symptomatic seizures Abnormality of the hair, Abnormality of the mouth, Abnormality of the nose, Abnormality of the palate, Abnormality of the teeth, Autistic behavior, Delayed speech and language development, Epicanthus, Hearing impairment, Hypertrichosis, Hypotelorism, Intellectual disability, Long eyebrows, Low-set ears, Macrocephaly, Motor delay, Symptomatic seizures XY NLGN4X chrx:g tcggcggt GGCCA>T Hemizygous Abnormality of the mouth, Abnormality of the skeletal system, Abnormality of the teeth, Aggressive behavior, Anteverted ears, Autistic behavior, Feeding difficulties, Hyperactivity, Hypertonia, Intellectual disability, Low-set ears, Microcephaly, Motor delay, Muscular hypotonia, Posteriorly rotated ears, Retrognathia, Sleep disturbance, Stereotypic behavior, Strabismus XY BCOR chrx:g g>a Hemizygous hand, Abnormality of the male genitalia, Abnormality of the mouth, Abnormality of the philtrum, Autistic behavior, Blindness, Decreased body weight, Delayed speech and language development, Downslanted palpebral fissures, Epicanthus, Facial asymmetry, Feeding difficulties, Hypertelorism, Intellectual disability, Mandibular prognathia, Microcephaly, Motor delay, Muscular hypotonia, Myopia, Neonatal hypotonia, Nystagmus, Ptosis, Stereotypic behavior, Strabismus XY SHROOM4 chrx:g catg>c Hemizygous Intellectual disability

19 XY ASCC3 chr6:g.chr6: a>ag Heterozygous XX CACNA1H chr16:g c>t Heterozygous Abnormality of the male genitalia, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Abnormality of the skeletal system, Abnormality of the teeth, Aggressive behavior, Anteverted ears, Decreased body weight, Delayed closure of the anterior fontanelle, Delayed speech and language development, Epicanthus, Hypermetropia, Hypertelorism, Hypertrichosis, Intellectual disability, Intrauterine growth retardation, Macrotia, Long eyebrows, Low anterior hairline, Low-set ears, Motor delay, Muscular hypotonia, Neonatal hypotonia, Pierre-Robin sequence, Short palm, Short stature, Sleep disturbance, Tapered finger, Thick vermilion border hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Abnormality of the teeth, Delayed speech and language development, Downslanted palpebral fissures, Hypertelorism, Intellectual disability, Low-set ears, Microcephaly, Micrognathia, Motor delay, Short stature, Stereotypic behavior, Symptomatic seizures

devseek (Sequence(Analysis(Panel(for(Neurodevelopmental(Disorders

devseek (Sequence(Analysis(Panel(for(Neurodevelopmental(Disorders ACSL4 Mental/retardation,/XBlinked/63 XLBR ADSL Adenylosuccinase/Deficiency AR AFF2 Mental/retardation,/XBlinked,/FRAXE/type XLBR ALG6 Congenital/disorder/of/glycosylation/type/Ic AR ANK3 Mental/retardation,/autosomal/recessive/37