Table 2 Genotypes and phenotypes of patients with SNVs/indels in STAG1, STAG2, and PDS5A identified in current study
From: Clinical exome sequencing reveals locus heterogeneity and phenotypic variability of cohesinopathies
Genes | STAG1 (NM_005862.2) | STAG2 (NM_006603.4) | PDS5A (NM_001100399.1) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patients | Patient 1 | Patient 2 | Patient 3 | Reported in Ref. 13 (n = 17) | Patient 7 | Patient 8 | Patient 9 | Patient 10 | Patient 11 | Reported in Ref. 14 (n = 1) | Patient 13 | |
Age at last exam | 11 years 5 months | 4 years 8 months | 4 years 2 months | 30 months to 33 years (median 7 years) | 3 years 8 months | 4 years 6 months | 11 years 1 month | 1 year 11 months | 5 years 3 months | 8 years | 2 years 6 months | |
Variant | c.2009_2012del (p.N670Ifs*25) | c.1129C>T (p.R377C) | c.253G>A (p.V85I): STAG1 c.1720-2A>G: ASXL1; | CNV deletion or SNVs/indels | c.418C>T (p.Q140*) | c.1605T>A (p.C535*) | c.1811G>A (p.R604Q) | c.1658_1660delinsT (p.K553Ifs*6) | c.476A>G (p.Y159C), hemizygous | c.205C>T p.(Arg69*) | c.2275G>T (p.E759*): PDS5A c.3325A>T (p.K1109*): ASXL3 | |
Critical gene(s) | STAG1 | STAG1 | ASXL1, STAG1 | STAG1 and othersa | STAG2 | STAG2 | STAG2 | STAG2 | STAG2 | STAG2 | ASXL3, PDS5A | |
Gender | F | M | F | 9 M/8 F | F | F | F | F | M | F | F | |
Inheritance | De novo | De novo | Both de novo | De novo or inherited | De novo | De novo | De novo | De novo | De novo | De novo | ASXL3: de novo; PDS5A: paternal | |
Growth | IUGR | - | NR | - | 3/17 | - | + | - | - | - | - | - |
Failure to thrive | - | + | - | 1/17 | NR | + | + | - | + | NR | + | |
Short stature | - | + | - | 5/17 | NR | + | + | + | + | + | + | |
Microcephaly | - | + | - | 4/17 | - | + | + | + | - | + | + | |
Development | Intellectual disability | + | NR | + | 17/17, mild to severe | NR | + | + | + | + | + | + |
Developmental delay | + | + | + | 17/17 | + | + | + | + | + | + | + | |
Autism spectrum disorder | NR | NR | + | 7/17 | NR | NR | NR | - | NR | - | - | |
Neurobehavioral | Behavioral problems | NR | + | + | NR | NR | + | NR | +, irritability | - | + | NR |
Seizures | NR | +, during infancy | + | 7/17 with epilepsy | Myoclonic movements | NR | NR | + | - | NR | - | |
Hypertonia | NR | - | - | NR | NR | NR | NR | - | - | NR | + | |
Hypotonia | NR | + | + | 4/17 | NR | + | + | + | + | NR | - | |
Craniofacial features | Brachycephaly | NR | NR | - | See footnotesb | - | + | NR | - | NR | See footnotesc | - |
Long curly eyelashes | + | NR | - | See footnotesb | NR | + | + | - | - | See footnotesc | NR | |
Synophrys | + | NR | + | See footnotesb | NR | - | - | - | - | See footnotesc | - | |
Anteverted nares | NR | NR | - | See footnotesb | NR | NR | + | + | - | - | ||
Depressed/broad nasal bridge | NR | + | + | See footnotesb | - | - | + | + | + | See footnotesc | + | |
Bulbous nasal tip | NR | NR | - | See footnotesb | - | NR | + | + | + | See footnotesc | - | |
Low-set ears | + | - | - | See footnotesb | NR | NR | - | + | + | See footnotesc | - | |
Dysmorphic ears | + | - | - | See footnotesb | + | + | + | + | + | See footnotesc | - | |
Long/smooth philtrum | - | NR | - | See footnotesb | NR | + | + | - | - | See footnotesc | - | |
High arched palate | NR | + | + | See footnotesb | - | - | NR | +, narrow | NR | See footnotesc | + | |
Thin upper lip | NR | NR | - | See footnotesb | + | + | + | - | + | See footnotesc | - | |
Downturned mouth | NR | NR | - | See footnotesb | NR | NR | + | -, small | - | See footnotesc | - | |
Cleft lip/palate | + | - | - | See footnotesb | - | - | NR | - | + | See footnotesc | - | |
Widely spaced teeth | NR | NR | + | See footnotesb | NR | NR | + | NA | - | See footnotesc | - | |
Micrognathia | NR | + | - | See footnotesb | NR | + | + | + | - | See footnotesc | - | |
Skin, nails, hair | Hypoplastic nails | - | NR | - | NR | + | NR | NR | +, with pits | - | NR | - |
Hirsutism | NR | NR | + | NR | NR | + | NR | - | - | NR | - | |
Hairline | NR | NR | - | NR | NR | Low, posterior | NR | NR | NR | low, anterior | - | |
Cutis marmorata | +, significant | NR | - | NR | NR | + | NR | - | - | NR | - | |
Ocular | Strabismus | + | NR | +, exotropia | NR | NR | + | NR | NR | - | NR | - |
Otolaryngologic | Hearing loss | - | - | - | NR | NR | +, conductive | NR | - | - | + | - |
Cardiovascular | Congenital heart defect | - | PDA | - | 1/17 | +, hypoplastic left heart, VSD, CA | NR | - | NR, no murmur | Minimal PFO, normal on follow-up | + | - |
Respiratory/thorax | Congenital diaphragmatic hernia | - | NR | - | NR | + | NR | +, right | - | NR | NR | - |
Pulmonary hypoplasia | - | NR | - | NR | NR | NR | +, right | - | - | NR | - | |
Gastrointestinal | Gastroesophageal reflux | NR | NR | - | 9/17 | +, Nissen and G-tube | + | + | - | - | NR | + |
Genitourinary/Renal Anomaly | Hypoplastic male genitalia | NA | + | NA | NR | NA | NA | NA | NA | - | NR | NA |
Cryptorchidism | NA | +, left | NA | 2/9 | NA | NA | NA | NA | - | NR | NA | |
Structural anomalies of the renal tract | - | +, horseshoe kidney | NR, not examined | NR | - | NR | NR | - | +, single kidney | NR | - | |
Musculoskeletal/ extremities | Scoliosis | - | - | - | 2/17 | + | NR | NR | + | + | NR | - |
Rib fusion | - | NR | - | NR | +, T4-5, T10-11, BL | NR | NR | + | - | NR | - | |
Vertebral anomalies | - | NR | - | NR | +, vertebral clefts | NR | +, vertebral clefts | + | - | NR | - | |
Arm/hand anomalies | - | + | - | NR | - | - | NR | - | NR | NR | - | |
Limited elbow extension | + | NR | - | NR | NR | NR | NR | - | NR | NR | - | |
Fifth finger clinodactyly | - | + | - | NR | NR | + | NR | - | NR | + | - | |
Single transverse palmar crease | NR | + | - | NR | - | + | NR | - | NR | NR | - | |
2–3 toe syndactyly | + | + | - | NR | - | + | NR | - | - | + | - | |
Studies and imaging | Abnormal brain MRI | + | + | + | 3/17 showed atrophy; other 3/17 showed unspecific anomaly | NR | NR | NR | + | Ectopic posterior pituitary, short pituitary stalk | + | +, mild |
Abnormal echocardiogram | - | NR | - | NR | + | NR | NR | NR | - | + | + | |
