Supplementary Online Content Tan TY, Dillon OJ, Stark Z, et al. Diagnostic effect and cost-effectiveness of whole-exome sequencing of ambulant children with suspected monogenic conditions. JAMA Pediatr. Published online July 31, 2017. doi:10.1001/jamapediatrics.2017.1755 etable. Clinical Phenotype and Genotype of Children Diagnosed by WES (n = 23) This supplementary material has been provided by the authors to give readers additional information about their work.
etable. Clinical Phenotype and Genotype of Children Diagnosed by WES (n = 23) ID Clinical phenotype (HPO terms) Diagnosis Gene Variant(s) Zygosity Inheritance 0204901 [HP:0004322] Short stature [HP:0000252] Microcephaly [HP:0000750] Delayed speech and language development [HP:0000664] Synophrys [HP:0000343] Long philtrum [HP:0000463] Anteverted nares 0204904 [HP:0000252] Microcephaly [HP:0002650] Scoliosis [HP:0001290] Generalized hypotonia [HP:0000664] Synophrys [HP:0001007] Hirsutism [HP:0003763] Bruxism [HP:0002019] Constipation [HP:0002360] Sleep disturbance 0204905 [HP:0004322] Short stature [HP:0000252] Microcephaly [HP:0000486] Strabismus [HP:0001537] Umbilical hernia [HP:0010864] Intellectual disability, severe [HP:0001290] Generalized hypotonia 0204902 [HP:0004322] Short stature [HP:0000252] Microcephaly [HP:0000664] Synophrys [HP:0000233] Thin vermilion border [HP:0000343] Long philtrum [HP:0004467] Preauricular pit [HP:0002342] Intellectual disability, moderate [HP:0004209] Clinodactyly of the 5th finger [HP:0001476] Delayed closure of the anterior fontanelle Cornelia De Lange Syndrome [OMIM 122470] Bainbridge-Ropers Syndrome [OMIM 615485] Autosomal recessive spastic paraplegia type 51 [OMIM 613744] KBG syndrome [OMIM 148050] NIPBL NM_015384.4:c.5471C>T;p.(Ser1824Leu) Heterozygous De novo ASXL3 NM_030632.2:c.1207C>T;p.(Gln403*) Heterozygous De novo AP4E1 ANKRD1 1 NM_007347.4:c.3277C>T;p.(Gln1093*) NM_007347.4:c.2129G>A;p.(Trp710*) NM_001256183.1:c.3224_3227delCTTT;p.( Glu1075Glyfs*242) Compound heterozygous Heterozygous AR De novo
0204914 [HP:0004325] Decreased body weight [HP:0004322] Short stature [HP:0010864] Intellectual disability, severe [HP:0001290] Generalized hypotonia [HP:0002188] Delayed CNS myelination [HP:0000369] Low-set ears [HP:0000490] Deeply set eye [HP:0000601] Hypotelorism 0204910 [HP:0000252] Microcephaly [HP:0001256] Intellectual disability, mild [HP:0001007] Hirsutism [HP:0000405] Conductive hearing impairment 0204915 [HP:0001513] Obesity [HP:0000098] Tall stature [HP:0001629] Ventricular septal defect [HP:0000047] Hypospadias [HP:0001256] Intellectual disability, mild [HP:0000193] Bifid uvula [HP:0011927] Short digit 0204920 [HP:0003323] Progressive muscle weakness [HP:0002240] Hepatomegaly [HP:0003236] Elevated serum creatine phosphokinase Mental retardation, autosomal dominant [OMIM 616944] Rubinstein-Taybi Syndrome [OMIM 613684] Acrodysostosis 2, with or without hormone resistance [OMIM 614613] Glutaric acidemia type IIC [OMIM 231680] TBL1XR 1 NM_024665.4:c.557C>T;p.(Ser186Leu) Heterozygous De novo EP300 NM_001429.3:c.1407delA;p.(Ala470Leu*8) Heterozygous De novo PDE4D NM_001165899.1:c.388T>C;p.(Phe130Leu) Heterozygous De novo ETFDH NM_004453.2:c.1456insT;p.(Leu486Profs*4 ) NM_004453.2:c.1238C>T;p.(Ser413Phe) Compound heterozygous AR
0204909 [HP:0000494] Downslanted palpebral fissures [HP:0000535] Sparse eyebrow [HP:0000156] High-arched palate [HP:0000463] Anteverted nares [HP:0010747] Medial flaring of the eyebrow [HP:0002162] Low posterior hairline [HP:0000508] Ptosis [HP:0000358] Posteriorly rotated ears [HP:0000369] Low-set ears [HP:0001212] Prominent fingertip pads [HP:0000768] Pectus carinatum [HP:0002650] Scoliosis [HP:0011342] Mild global developmental delay [HP:0006610] Wide intermamillary distance [HP:0003186] Inverted nipples 0204924 [HP:0004325] Decreased body weight [HP:0004322] Short stature [HP:0000154] Wide mouth [HP:0000637] Long palpebral fissure [HP:0000666] Horizontal nystagmus [HP:0001156] Brachydactyly syndrome [HP:0001382] Joint hypermobility [HP:0011968] Feeding difficulties [HP:0011343] Moderate global developmental delay [HP:0001250] Seizures [HP:0010832] Abnormality of pain sensation [HP:0011398] Central hypotonia [HP:0010780] Hyperacusis Coffin Siris Syndrome 2 [OMIM 614607] Mental retardation, autosomal dominant [OMIM 616944] ARID1A NM_006015.4:c.2367_2368delGCinsTT Heterozygous De novo TBL1XR 1 NM_024665.4:c.976A>C;p.(Ser326Arg) Heterozygous De novo
0204927 [HP:0000490] Deeply set eye [HP:0011228] Horizontal eyebrow [HP:0000322] Short philtrum [HP:0000639] Nystagmus [HP:0000565] Esotropia [HP:0000377] Abnormality of the pinna [HP:0009748] Large earlobe [HP:0002783] Recurrent lower respiratory tract infections [HP:0010864] Intellectual disability, severe [HP:0003763] Bruxism [HP:0002360] Sleep disturbance [HP:0001332] Dystonia [HP:0002072] Chorea [HP:0002599] Head titubation [HP:0002453] Abnormality of the globus pallidus [HP:0002019] Constipation [HP:0001007] Hirsutism [HP:0008936] Muscular hypotonia of the trunk 0204930 [HP:0004322] Short stature [HP:0001956] Truncal obesity [HP:0000823] Delayed puberty [HP:0000637] Long palpebral fissure [HP:0010044] Short 4th metacarpal [HP:0004704] Short fifth metatarsal [HP:0010041] Short 3rd metacarpal [HP:0010047] Short 5th metacarpal [HP:0004689] Short fourth metatarsal [HP:0000729] Autism spectrum disorder [HP:0001249] Intellectual disability [HP:0001250] Seizures Mental retardation, autosomal dominant 8 [OMIM 614254] Albright hereditary osteodystrophy-like Syndrome [OMIM 610087] GRIN1 NM_007327.3:c.1676A>G;p.(Gln559Arg) Heterozygous De novo PRMT7 NM_019023.2:c.312delG;p.(Lys105Argfs*2 2) NM_019023.2:c.1159A>G;p.(Arg387Gly) Compound heterozygous AR
0204929 [HP:0004325] Decreased body weight [HP:0004322] Short stature [HP:0001883] Talipes [HP:0002999] Patellar dislocation [HP:0003083] Dislocated radial head [HP:0001156] Brachydactyly syndrome [HP:0001172] Abnormality of the thumb [HP:0002751] Kyphoscoliosis 0204925 [HP:0000490] Deeply set eye [HP:0000347] Micrognathia [HP:0000343] Long philtrum [HP:0000219] Thin upper lip vermilion [HP:0002007] Frontal bossing [HP:0000316] Hypertelorism [HP:0000248] Brachycephaly [HP:0002714] Downturned corners of mouth [HP:0000431] Wide nasal bridge [HP:0007598] Bilateral single transverse palmar creases [HP:0001762] Talipes equinovarus [HP:0006055] Ulnar deviated club hands [HP:0001840] Metatarsus adductus [HP:0005617] Bilateral camptodactyly [HP:0004209] Clinodactyly of the 5th finger [HP:0005684] Distal arthrogryposis 0204932 [HP:0000252] Microcephaly [HP:0009765] Low hanging columella [HP:0011819] Submucous cleft soft palate [HP:0000494] Downslanted palpebral fissures Spondyloepiphyseal dysplasia with congenital joint dislocations [OMIM 143095] Aarskog-Scott Syndrome [OMIM 305400] Weidemann-Steiner Syndrome [OMIM 605130] CHST3 NM_004273.4:c.1291dupA;p.(Ser431Lysfs* 81) Homozygous FGD1 NM_004463.2:c.1171A>G;p.(Arg391Gly) Hemizygous XLR; mat KMT2A NM_001197104.1:c.3539G>C;p.(Gly1180Al a) Heterozygous AR De novo
[HP:0000319] Smooth philtrum [HP:0000233] Thin vermilion border [HP:0000565] Esotropia [HP:0000365] Hearing impairment [HP:0011304] Broad thumb [HP:0010055] Broad hallux [HP:0001182] Tapered finger [HP:0011342] Mild global developmental delay [HP:0001290] Generalized hypotonia [HP:0001007] Hirsutism [HP:0004780] Elbow hypertrichosis 0204931 [HP:0002209] Sparse scalp hair [HP:0001019] Erythroderma [HP:0008064] Ichthyosiform abnormality of the skin [HP:0007479] Congenital nonbullous ichthyosiform erythroderma [HP:0000964] Eczema [HP:0002020] Gastroesophageal reflux 0204934 [HP:0007565] Multiple cafe-au-lait spots [HP:0100255] Metaphyseal dysplasia [HP:0001875] Neutropenia [HP:0002019] Constipation 0204926 [HP:0008066] Abnormal blistering of the skin [HP:0000977] Soft skin [HP:0000750] Delayed speech and language development Ichthyosis, congenital, autosomal recessive 6 [OMIM 612281] Schmid metaphyseal chondrodysplasia [OMIM 156500] Epidermolysis bullosa simplex, Ogna type [OMIM 131950] NIPAL4 NM_001099287.1:c.527C>A;p.(Ala176Asp) Homozygous AR COL10A 1 NM_000493:c.1945C>T;p.(Gln649*) Heterozygous De novo PLEC NM_000445.3:c.5998C>T;p.(Arg2000Trp) Heterozygous AD (inherited from affected mother)
0204938 [HP:0004322] Short stature [HP:0000535]Sparse eyebrow [HP:0006297] Hypoplasia of dental enamel [HP:0004422] Biparietal narrowing [HP:0000675] Macrodontia of permanent maxillary central incisor [HP:0000396] Overfolded helix [HP:0001500] Broad finger [HP:0001764] Small feet [HP:0010055] Broad hallux [HP:0008440] C1-C2 vertebral abnormality [HP:0001256] Intellectual disability, mild [HP:0002557] Hypoplastic nipples [HP:0000998] Hypertrichosis [HP:0001319] Neonatal hypotonia 0204940 [HP:0002209] Sparse scalp hair [HP:0000280] Coarse facial features [HP:0001344] Absent speech [HP:0011344] Severe global developmental delay [HP:0008398] Hypoplastic fifth fingernail [HP:0000998] Hypertrichosis Weidemann-Steiner Syndrome [OMIM 605130] Coffin-Siris Syndrome 1 [OMIM 135900] KMT2A ARID1B NM_001197104.1:c.2312delC;p.(Pro773Arg fs*8) NM_020732.3:c.3555dupC;p.(Ser1186Leufs *24) Heterozygous Heterozygous De novo De novo
0204429 [HP:0000252] Microcephaly [HP:0000601] Hypotelorism [HP:0000455] Broad nasal tip [HP:0005288] Abnormality of the nares [HP:0000582] Upslanted palpebral fissure [HP:0011480] Unilateral microphthalmos [HP:0000589] Coloboma [HP:0000486] Strabismus [HP:0000412] Prominent ears [HP:0009748] Large earlobe [HP:0000377] Abnormality of the pinna [HP:0100872] Abnormality of the plantar skin of foot [HP:0001031] Subcutaneous lipoma [HP:0000960] Sacral dimple [HP:0004209] Clinodactyly of the 5th finger [HP:0010864] Intellectual disability, severe [HP:0003763] Bruxism [HP:0002191] Spasticity, progressive [HP:0002019] Constipation 0204430 [HP:0004322] Short stature [HP:0000256] Macrocephaly [HP:0002910] Elevated hepatic transaminases [HP:0003119] Abnormality of lipid metabolism [HP:0002240] Hepatomegaly 0204457 [HP:0000639] Nystagmus [HP:0008024] Congenital nuclear cataract [HP:0011344] Severe global developmental delay [HP:0001332] Dystonia Mental retardation, autosomal dominant 19 [OMIM 615075] Glycogen storage disease IXa1 [OMIM 306000] Autosomal recessive spastic paraplegia 46 [OMIM 614409] CTNNB1 PHKA2 NM_001904.3:c.2050delA;p.(Arg684Glufs* 51) NM_000292.2:c.3337-1dupG [2.8 kb del chrx: 18,912,524-18,915,343 identified on custom PCR and Sanger sequencing confirmation] Heterozygous Hemizygous GBA2 NM_020944.2:c.1495G>A;p.(Glu499Lys) Homozygous AR De novo XLR
[HP:0001276] Hypertonia [HP:0100702] Arachnoid cyst Legend: AD autosomal dominant; AR autosomal recessive; HPO Human Phenotype Ontology; OMIM Online Mendelian Inheritance in Man; XLR X-linked recessive.