Table 3.
FOXP1 single nucleotide variants (SNVs) identified in one individual from this cohort (Family 38) and 7 additional (cases 2-8 from clinical WES database) individuals with pathogenic novel de novo SNVs. Six out of eight cases have syndromic form of kidney and genitourinary tract defects. This strongly suggests an important role for FOXP1 in Kidney and GU tract development.
| Case Number | Genome build | Chr: position | SNV | Protein change | CADD score | Frequency in ExAc | Number of LOF in ExAc | Segregation | Phenotype |
|---|---|---|---|---|---|---|---|---|---|
| Case 1 (Family 38) | Hg19 | 3: 71090675 | c.C673A | p. P225T | 24.7 | 0 | 2 | De Novo | Hydrocephaly, GDD and unilateral renal agenesis |
| Case 2 | Hg19 | 3: 71027085 | c.1240_1241del | p.L414fs | 35 | 0 | 2 | De Novo | Hydrocephaly, brain atrophy, seizure, DD, VSD, neurogenic bladder, hydronephrosis, tethered cord, and behavior problems |
| Case 3 | Hg19 | 3: 71090502 | c.844-845del | p.V283fs | 35 | 0 | 2 | De Novo | Bilateral ventricular enlargement of brain, ID, DD, hypotonia, horseshoe kidney, UDT, hypospadias, and facial dysmorphic features |
| Case 4 | Hg19 | 3: 71021784 | c. 1574G>A | p. R525Q | 34 | 0 | 2 | De Novo | GDD, mega cisterna magna, seizure, hypotonia, concealed penis, retractable testis, and skeletal abnormalities |
| Case 5 | Hg19 | 3: 71021815 | c.1543C>G | p.H515D | 27.7 | 0 | 2 | De Novo | GDD, hip contractures, dysmorphic features, short stature, mild scoliosis, abnormally positioned thumbs, dysmorphic features, and UDT |
| Case 6 | Hg19 | 3: 71019958 | c.1653-2A>T | N/A | 24.8 | 0 | 2 | De Novo | DD, ataxia, mild distal arthrogryposis, ASD, dysmorphic facial features, strabismus, vertical nystagmus and snoring, right duplicated collecting system, and trabeculation of the posterior urinary bladder wall |
| Case 7 | Hg19 | 3: 71027034 | c.1291_1292del | p.T431fs | 35 | 0 | 2 | De Novo | Macrocephaly, GDD, ID, dysmorphic features, hyperextensibility, joint contractures (3rd finger camptodactyly), droopy eyelids, and two cafe au lait spots |
| Case 8 | Hg19 | 3: 71021735 | c.1606_1622dup | p.F541fs | 35 | 0 | 2 | De Novo | Structural brain abnormalities, GDD, aggressive behavior and hyperactivity, hyperopic astigmatism, hypotonia, and ankle tightness |
ASD, atrial septal defect; CADD, Combined Annotation Dependent Depletion; Chr, chromosome , DD, developmental delay; ExAc, Exome Aggregation Consortium; GDD, global developmental delay; ID, intellectual disability; LOF, loss-of-function; UDT, undescended testis; VSD, ventricular septal defect