Table 1.
Clinical and molecular features of patients with intragenic pathogenic LoF BCAP31 variants.
| Patient ID | Literature | This report | Total | This report | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 6 pat, 4 families | P1 Family 1 | P2 Family 2 | P3 Family 2 | P4 Family 3 | P5 Family 4 | P6 Family 5 | P7 Family 6 | P8 Family 7 | P9 Family 8 | P10 Family 9 | P11 Family 10 | P12 Family 11 | 18 males 15 families | P13 (female) Family 12 | |
| Age at last examination | 3–22y | 2y3m | 21y6m | 10y6m | 2y6m | 2y6m | 28y | 14y | 5y9m | 9y7m | 4y7m (died 4y9m) | 8y11m | 2y10m | Median 9y1m | 7y5m |
| BCAP31 variant | c.3G>C | c.92+1G>A | c.92+1G>A | c.466C>T | c.365_366del | c.445A>T | c.664dup | c.702+1G>A | c.733_736del | c.365_366del | c.705_*4del | NC_000023.9: g.(152982315_152988064)del | c.380_383dup | ||
| Inheritance | 2 de novo others inherited | mat | mat | mat | mat | mat | mat | mat | de novo | mat | mat (de novo in mother) | nd | mat (mosaic) | 3 de novo in 15 families | mat (mosaic) |
| Affected carrier mother | 1 SNHL | − | SNHL | LD mild ID | SNHL | − | − | nr | − | − | nd | Episodes of nystagmus | 3 SNHL 1 mild ID | − | |
| Severity of DD/ID | 6/6 severe to profound | Severe | Severe | Severe | Severe | Severe | Severe | Severe | Severe/profound | Profound | Profound | Severe | Severe | 18/18 severe to profound | Severe |
| Walking | 0/6 | − | − | − | − | − | − | − | − | − | − | − | − | 0/18 | +4y |
| Absent language | 6/6 | + | + | + | + | + | + | + | + | + | + | + | + | 18/18 | − |
| Seizures | 3/6 | − | − | − | − | − | + | +Febrile | − | + | − | − | − | 6/18 | − |
| Dystonia/chorea | 6/6 | + | + | + | + | + | + | + | + | + | + | + | + | 17/18 | − |
| Spasticity | 5/5 | − | − | − | − | + | + | + | + | nd | + | + | − | 11/16 | + |
| Hearing loss | 6/6 | +SNHL | +SNHL | − | nd | +SNHL | + | nd | +Mixed | + | +SNHL | +SNHL | +SNHL | 16/18 | + |
| OFC < −2 SD | 5/6 | −(−2 SD) | − | +(−3 SD) | +(−5 SD) | +(− 4 SD) | −(−2 SD) | − | +(−2,2 SD) | nd | +(−7 SD) | +(−3,5 SD) | +(−3 SD) | 13/18 | +(−3, 5 SD) |
| Elevated liver enzyme | 4/4 | − | +(C) | +(I) | +(I) | + | − | + (C) | +(I) | +(I) | +(C) | +(C) | +(C) | 14/16 | nd |
| Unexplained episodic fever | 3/3 | − | − | − | + | − | + | − | − | nd | + | − | − | 6/14 | − |
| Age at MRI | 2y | 9m, 10y, 12y | 5m | 15m | 3y | nd | 11y | 8m | 8m | 5m, 15m | 8m | 3m | 3, 5y | ||
| Abnormal WM | 4/4 | + | + at 9m nl at 12y | nd | + | + | − | + | + | − | − | + | − | 11/15 | − |
| Other MRI findings |
4 Cortical atrophy 1 CC atrophy 2 abN BG 1 Cerebellar atrophy |
abN BG | VH | nd | − | Cortical atrophy, thin CC | VH | Cortical atrophy, thin CC, abN BG | Cortical atrophy, thin CC | Cortical atrophy | − | − | − | Thin CC, enlarged CM and subA spaces | |
Reference transcript: NM_001139441.1.
abN abnormal, BG basal ganglia, C chronic, CM cisterna magna, CC corpus callosum, G gastrostomy tube, ID intellectual disability, I intermittent, LD learning disabilities, mat maternal, nd not determined, nr non relevant, P patient, SNHL sensorineural hearing loss, subA subarachnoidal, WM white matter, VH vermis hypoplasia.