Table I.
Summary of genetic findings and clinical features of RSRC1 patients
| Family | Family I (Amish) | Family II (Persian) | Family III (Pakistani) | Family IV (Saudi) | Family V (EUR/ ME) | Family VI (Pakistani) | Family VII (Egyptian) | Maddirevula et al.2018 (Malaysian) | Perez et al.2018 (Bedouin) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient | 1(II-2) | 2(II-3) | 3(II-4) | 4(II-5) | 5(II-3) | 6(II-1) | 7(II-2) | 8(II-2) | 9(II-1) | 10(II-2) | 11(II-1) | 12(II-6) | 13(II-4) | 14(II-3) | 15(II-5) | 16 (II-8) | 17(II-9) | 3 patients | 5 patients |
| Age/sex | 3 y/F | 6 y/M | 5 y/M | 11 mo/M | 6 y/M | 14 y/F | 3 y/F | 9 y/M | 11 y/M | 4 y/M | 16 y/F | 6 y/F | 15 y/M | 16 y/F | 22 y/F | 16 y/F | 12 y/F | 4–10 y/2M, 1F | 0.5–8 y/3F, 2M |
| Homozygous RSRC1 variants [NM_001271838.1] | c.158,256,914_158,338,237dela | c.784 C>T (p.Gln262*) | c.157,839,811_ 157,840, 314delb | c.250 C>T (p.Arg84*) | c.441_447dupAGAAAAG (p.Glu150Argfs*6) | c.532-1 G>A | c.3G>T(p.Met1?) | c.268C>T (p.Arg90*) | c.205C>T (p.Arg69*) | ||||||||||
| Consanguinity | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + (3) | + (5) |
| Dysmorphic features | + | + | + | + | + | + | + | – | – | + | + | + | + | + | – | – | – | – | + (5) |
| Global DD/ID | + | + | + | + | ++ | ++ | + | ++ | ++ | + | + | ++ | ++ | ++ | ++ | ++ | ++ | + (5) | +/++ (5) |
| Speech delay | N/A | + | + | + | N/A | N/A | N/A | N/A | N/A | + | + | + | + | – | – | + | – | + (1) | + (4) |
| Behavioural abnormalities | – | ASD | ADHD, ASD | – | ASD | ASD | ASD | ADHD | ADHD | – | SCT | Agg | Agg | SCT | ASD | Agg | ASD | – | TT (4), ASD (1), ADHD (4) |
| Hypotonia | +++ | ++ | + | ++ | ++ | ++ | ++ | + | + | + | ++ | + | + | + | + | + | + | – | + (5) |
| Movement disorders | – | Gait ataxia | Gait ataxia | – | Gait ataxia | Gait ataxia | – | – | – | Truncal ataxia | Brady-kinesia, ataxic gait | – | – | – | – | – | – | – | Fine motor impairment (4) |
| Seizures | – | – | – | – | N/A | – | FS, GTCS | FS | – | GTCS | – | FS, GTCS | FS, GTCS | N/A | – | – | FS | FS (1) | FS (5), epilepsy (1) |
| Musculo-skeletal abnormalities | – | PP, CV | PP, CV | – | – | – | – | PP | PP | – | PP, CV, short toes | PP, short fifth toes | CV, genu valgum | PP | PP | PP | – | Foot deformities (2) | – |
| Brain MRI | N | PSS | PSS | N/A | MCA | N | N | N | N | Left temporo- parietal atrophy | N | N/A | N/A | N/A | N | N | N | Temporal lobes atrophy (1) | N (5) |
ADHD = attention deficit hyperactivity disorder; Agg = aggressive; ASD = autism spectrum disorder; CV = cubitus valgus; DD = developmental delay; EUR = European; FS = febrile seizures; GTCS = generalized tonic-clonic seizures; ID = intellectual disability (+, mild; ++, moderate); MCA = mild cerebral atrophy; ME = Middle Eastern; mo = months; N = normal; N/A = not available; PP = pes planus; PSS = prominent subarachnoid spaces; SCT = sluggish cognitive tempo; y = years.
a
hg19; 81-kb deletion encompassing exons 9–10 of RSRC1 and whole MLF1.
b
hg19; 500-bp deletion encompassing exon 2 of RSRC1.