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Table 2 Summary of clinical features observed in the atypical cases detected by gene panel testa

From: Comprehensive gene panels provide advantages over clinical exome sequencing for Mendelian diseases

   Mutation      Observed phenotype compared with published phenotype(s)
Sample ID Gene name Type Status Origin Type of panel Published phenotype(s) related to the case Typical/previously reported feature(s) Atypical feature(s)
DG08RC00033 FGFR2 Missense HTZ De novo DD Craniosynostosis syndromes Craniofacial anomalies Upper eyelid coloboma
      Sacrococcygeal tail  
NM_000141.4: c.870G > C (p.Trp290Cys) Syndactyly  
Neonatal teeth(with Beare-Stevenson cutis gyrata syndrome)
Choanal atresia
Thinning of the genu of corpus callosum (with Pfeiffer syndrome)
11DG0118 HRAS Missense HTZ De novo DD Costello syndrome Dysmorphic facies Corneal haziness
NM_005343.2: c.34G > A (p.Gly12Ser) Multiple joint dislocations Tracheomalacia and bronchomalacia
10DG1851 COL2A1 Missense HTZ De novo DD Spondylometaepiphyseal dysplasia Disproportionate short stature Valvular disease (mild TR, MR)
Thoracic dextroscoliosis Acanthosis nigricans
Metaphyseal dysplasia
NM_033150.2: c.3023G > T (p.Gly1008Val) Inguinal hernia
09DG01603 TCOF1 Nonsense HMZ Inherited DD Treacher Collins syndrome 1 Underdevelopment zygoma Confirmed to be inherited as AR
  Choanal atresia
NM_001008657.2: c.2656C > T (p.Gln886*) Microtia
No external auditory meatus
Malformed ossicles and semicircular canal
Iris/optic disc coloboma
10DG1847 BRAF Missense HTZ De novo DD Cardiofaciocutaneous syndrome Hypotonia Coarse face similar to Costello syndrome
NM_004333.4: c.1789C > G (p.Leu597Val) Speech delay No cardiac defects
Acanthosis nigricans
Deep palmar and plantar creases
12DG0359 EP300 Nonsense HTZ De novo DD Rubinstein-Taybi syndrome 2 None Atypical dysmorphic facies
Microcephalic primordial dwarfism
NM_001429.3: c.1092C > A (p.Cys364*)
11DG2179 NFIX Nonsense HTZ Unknown DD Sotos syndrome type 2 Overgrowth Marfanoid habitus
(Father was not tested) GDD Normal bone age
NM_001271043.2: c.544G > T (p.Glu182*)
13DG0355 GNS Frameshift HMZ Inherited DD Mucopolysaccharidosis type IIID Mild coarse face Advanced RP
NM_002076.3: c.83del (p.Leu28Argfs*37)    Mild hepatomegaly
Clear cornea
Skeletal manifestations
11DG2478 COL11A2 Missense HMZ Inherited DD Otospondylomegaepiphyseal dysplasia Epiphyseal dysplasia Hypoplastic optic nerve
NM_001163771.1: c.654 T > A (p.Tyr218*)     Mitral valve prolapse and regurgitation
14DG1212 IFT122 Splice site HMZ Inherited DD Cranioectodermal dysplasia 1 Nystagmus Iris and optic nerve coloboma
Metaphyseal dysplasia Microphthalmia
NM_052990.2:c.2042 + 2 T > C Duplicated thumb and big toe
Post-axial polydactyly
Very short tibiae compared with fibulae
13DG2208 ROR2 Missense HMZ Parents not tested DD Robinow syndrome Vertebral anomalies(in Robinow syndrome) Atypical fibrochondrogenesis-like skeletal dysplasia
NM_004560.3: c.1970G > A (p.Arg657His) Brachydactyly, type B1
10DG0298 KMT2A Frameshift HTZ De Novo DD Wiedemann-Steiner syndrome Dysmorphic facies Absent uterus and vagina, remarkable clitoromegaly
NM_001197104.1: c.7567_7570del (p.Val2523Lysfs*2)
08DG-00226 NSD1 Nonsense HTZ De Novo DD Sotos Syndrome 1 Dysmorphic facies No overgrowth
NM_022455.4: c.2058 T > A (p.Tyr686*) Thin corpus callosum, PVL and colpocephaly on MRI brain
10DG0615 CNNM4 Missense HMZ Parents not tested Vision Jalili syndrome LCA, retinal degeneration Retinal coloboma
NM_020184.3: c.734C > T (p.Ser245Leu)     No dental anomalies
12DG0398 BBS4 Frameshift Compound HTZ Parents not tested Vision Bardet-Biedl syndrome 4 -RP Lack of other features of BBS
NM_001252678.1:c.795_796insT(p.Lys266*) (isolated RP)
NM_033028.4:c.262delG (p.Glu88Asnfs*54)  
14DG0073 ATRX Nonsense Hemizygous Inherited Neuro Mental retardation-hypotonic facies syndrome, X-linked Microcephaly RP
NM_000489.3:c.7156C > T (p.Arg2386*) GDD Optic disc coloboma
White matter changes
12DG1296 ALMS1 Frameshift HMZ Inherited Vision Alstrom syndrome Achromatopsia Lack of other features of Alstrom syndrome (isolated achromatopsia)
NM_015120.4: c.1674delT (p.Pro559Leufs*37)
12DG1554 STXBP1 Missense HTZ De novo Neuro Epileptic encephalopathy, early infantile, 4 Seizures Pigmentary retinal changes
   NM_001032221.3: c.874C > T (p.Arg292Cys)     
13DG1051 CDKL5 Nonsense HMZ Inherited Neuro Epileptic encephalopathy, early infantile, 2 GDD Macrocephaly and overgrowth
NM_001037343.1: c.2854C > T (p.Arg952*) Facial dysmorphism similar to Sotos syndrome but normal bone age and negative NSD1 mutation
No seizures or regression
No abnormal movements
10DG2024 GTDC2 Missense HMZ Inherited Neuro Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8) None Isolated large occipital encephalocele
(POMGNT2) No polydactyly
NM_032806.5: c.473G > A (p.Arg158His)     Neonatal death
12DG0133 HSD17B4 Missense HMZ Inherited Neuro D-bifunctional protein deficiency Neonatal seizures Normal brain MRI
No skeletal manifestations or stippling
NM_001199291.1: c.442C > G (p.His148Asp) No eye findings
No dysmorphism
10DG0415 ATN1 Missense HTZ De novo Neuro Dentatorubro-pallidoluysian None Early onset static encephalopathy
NM_001940.3: c.3178C > T (p.His1060Tyr) atrophy   Novel molecular mechanism (point mutation)
12DG0705 KIAA0196 Missense HTZ De Novo Neuro Ritscher-Schinzel syndrome Seizures Normal brain MRI
NM_014846.3: c.1669G > A (p.Ala557Thr)   Spastic paraplegia 8, AD Speech delay and learning disability No ataxia or spasticity
10DG0351 ADRA2B Nonsense HMZ Inherited Neuro Non-syndromic ID None Microcephaly
NM_000682.6: c.664C > T (p.Arg222*) GDD
12DG0532 ZNF526 Missense HMZ Inherited Neuro Mild non-syndromic ID None Novel Noonan like phenotype
NM_133444.1: c.479A > C (p.Lys160Thr)
14DG0745 WDR45B Nonsense HMZ Inherited Neuro ID and microcephaly Primary microcephaly Epilepsy
(WDR45L) NM_019613.3: c.673C > T (p.Arg225*) White matter changes, brain atrophy, hypoplastic corpus callosum
13DG2156 WDR81 Nonsense HMZ Inherited Neuro Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2 Cerebellar hypoplasia Normal corpus callosum
NM_152348.3: c.133C > T (p.Gln45*) Prenatal onset complicated by neonatal death
  1. aAtypical case is defined as a case that has unusual clinical features, unusual mode of inheritance, a novel phenotype or lack of typical features
  2. AD, autosomal dominant, AR, BBS Bardet-Biedl syndrome, DD Dysmorphia-Dysplasia panel, FTT failure to thrive, GDD global developmental delay, HMZ Homozygous, HTZ Heterozygous, ID intellectual disability, LCA, Leber congenital amaurosis, MR, MRI magnetic resonance imaging, PVL, Periventricular leukomalacia, RP retinitis pigmentosa, TR, Tricuspid regurgitation