Table 1.
Genotypes and phenotypes of the patients diagnosed in the study. Only the most striking phenotypic features are listed. Table S1 contains the full phenotypic spectrum of the diagnosed patients as well as reported phenotypic spectrums associated with the diagnosed syndromes
| Patient ID; Age; Gender; Diagnosis | Phenotypic Features (HPO terms) | Genotype a ; Pathogenicity b ; Segregation |
|---|---|---|
| Patient 1; 14y; m; Rubinstein–Taybi syndrome 2, RSTS2; AD (MIM 613684) | Intellectual disability, moderate (HP:0002342), Facial grimacing (HP:00002273), Growth delay (HP:0001510), Bilateral cryptorchidism (HP:0008689), Microcephaly (HP:0000252), Narrow palpebral fissures (HP:0000581), Dental crowding (HP:0000678),), High, narrow palate (HP:0002705), Abnormality of the fingertips (Square)(HP:0001211) | EP300,NM_001429.3: c.[5783dup];[=], p.(Met1928Ilefs*145), novel;probably pathogenic, MAF = 0; de novo |
| Patient 2; 8.5y, m; Spastic Paraplegia 50, SPG50; AR (MIM 612936) | Intellectual disability, severe (HP:0010864), Seizures (HP:0001250), Generalized hypotonia (HP:0001290), Microcephaly (HP:0000252), Tapered fingers (HP:0001182), Abnormal myelination (HP:0012447) | AP4M1, NM_004722.2: c.[566del];[916C > T]; p.(Leu189Trpfs*10)/ p.(Arg306*); novel/known (ClinVar:RCV000680158.1); pathogenic/probably pathogenic MAF = 0/ MAF = 0.000039 (GnomAD); paternal/maternal |
| Patient 3; 4y; f; Wiedemann–Steiner syndrome, WDSTS; AD (MIM 605130) | Intellectual disability, moderate (HP:0002342), Failure to thrive (HP:0001508), Muscular hypotonia (HP:0001252)/Generalized hypotonia (HP:0001290), Localized hirsutism (HP:0009889), Thin upper lip (HP:0000219), Clinodactyly of the fifth fingers (HP:0004209), Tapered fingers (HP:0001182) | KMT2A, NM_001197104.1: c.[4012 + 2T>A];[=]; p.?;novel; probably pathogenic (the substitution is located in the donor splice site,MaxEnt: −100.0%, NNSPLICE: −100.0%, SSF: −100.0%), MAF = 0; de novo |
| Patient 4; 5y; f;Cornelia de Lange syndrome 2, CDLS2; XLD (MIM 300590) | Intellectual disability, severe (HP:0010864), Growth delay (HP:0001510), Seizures (HP:0001250)/EEG abnormality (HP:0002353), Hyperactivity (HP:0000752), Hirsutism (HP:0001007), Microcephaly (HP:0000252), Arched eyebrows (HP:0002553), Anteverted nares (HP:0000463) | SMC1A, NM_006306.3: c.[238G > T];[=], p.(Val80Phe); novel; probably pathogenic (SIFT: Deleterious, MutationTaster: disease causing), MAF = 0; de novo |
| Patient 5; 14y; f; Glass syndrome; AD (OMIM 612313) | Intellectual disability, severe (HP:0010864), Marfanoid habitus (HP:0001519), Scoliosis (HP:0002650), Synophrys (HP:0000664), Long fingers (HP:0100807) | SATB2: NM_015265.3:c.[716del];[=], p.(Arg239Glnfs*20), novel; probably pathogenic; de novo |
| Patient 6; 10y; m; Bosch–Boonstra–Schaaf optic atrophy syndrome, BBSOAS; AD (MIM615722) | Intellectual disability, severe (HP:0010864), Cerebral palsy (HP:0100021), Seizures (HP:0001250), Gait imbalance (HP:0002141), Recurrent infections (HP:0002719), Narrow hands (HP:0004283), Narrow foot (HP:0001786) | NR2F1, NM_005654.5: c.[1217T > C];[=]; p.(Met406Thr); known (ClinVar: RCV000477887.1); probably pathogenic (MutationTaster: disease causing), MAF = 0; de novo |
| Patient 7; 7.5y; m; Cerebral creatine deficiency syndrome 1, SLC6A8; XLR (MIM300352) | Intellectual disability, moderate (HP:0002342), Autism (HP:0000717), Increased muscle tone (HP:0001276), Velvety skin (HP:0000977), Hyperextensibility of the finger joints (HP:0001187) | SLC6A8, NM_005629.3: c.[224T > C];[=];p.(Val75Ala);missense, novel;probably pathogenic; de novo |
| Patient 8; 4y; f; Mental retardation, autosomal dominant 31, MRD31; AD (MIM 616,158) | Intellectual disability (HP:0001249), Self‐injurious behavior (HP:0100716), Obesity (HP:0001513), Muscular hypotonia (HP:0001252), Loose skin (HP:0000973) | PURA, NM_005859.4: c.[3G > A];[=];p.?; start loss, novel; probably pathogenic (SIFT: Deleterious, MutationTaster: disease causing), MAF = 0; de novo |
a
The nomenclature of molecular variants follows the Human Genome Variation Society guidelines (HGVS, http://varnomen.hgvs.org/) using human cDNA sequences from RefSeq database.
b
Molecular variants were assessed by pathogenicity prediction tools: SIFT and MutationTaster software for nucleotide changes localized in coding sequence, and MaxEnt, NNSPLICE or SSF for nucleotide changes identified in intronic sequence. ClinVar database was search for known pathogenic variants (https://www.ncbi.nlm.nih.gov/clinvar/). The minor allele frequency (MAF) as recorded in ExAC and GnomAD databases.