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 | |||||||
Myopia | ||||||||
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 | |||||||
Deafness | ||||||||
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 |
GDD | ||||||||
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 | |||||||