Table 1.
Patient phenotypes compared to those described in literature
| This report (Family I) | This report (Family I) | This report (Family II) | This report (Family II) | This report (Family II) | This report (Family II) | This report (Family II) | Palmer (2016) | Alazami (2015) | Alazami (2015) | Alazami (2015) | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient number | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | IV:4 | DG08RC00075/X:2 | DG08RC00076/IX:8 | DG08RC00077I/IX:7 |
| Relation to the proband | Proband | Sibling | Cousin | Cousin | Cousin | Sister | Proband | Proband | Proband | 2nd-Cousin | 2nd-Cousin |
| Mutation (NM_022786.2)a | c.674−2A>T | c.674−2A>T | c.294+1G>Ab | c.294+1G>A | c.294+1G>A | c.294+1G>A | c.294+1G>A | c.294+1G>A | c.565G>A | c.565G>A | c.565G>A |
| Mutation (NP_073623.1) | p.Thr266_Phe271delc | p.Thr266_Phe271delc | p.Lys59_Asn98del | p.Lys59_Asn98del | p.Lys59_Asn98del | p.Lys59_Asn98del | p.Lys59_Asn98del | p.Lys59_Asn98del | p.Gly189Arg | p.Gly189Arg | p.Gly189Arg |
| Inheritance | AR | AR | AR | AR | AR | AR | AR | AR | AR | AR | AR |
| Gender | Female | Female | Male | Male | Female | Female | Female | Female | Male | Female | Male |
| Age | 17y | 2y 5mo | 15 mo (died) | 5y (died) | 2y 5mo (died) | 2y 3mo (died) | 3y 2mo (died) | 1y (died) | 25y | 8y | 13y |
| Ethnicity | Mexican American | Mexican American | Lebanese Australian | Lebanese Australian | Lebanese Australian | Lebanese Australian | Lebanese Australian | Lebanese Australian | Saudi | Saudi | Saudi |
| Consanguinity reported | No | No | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Epileptic encephalopathy | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Seizure onset | 6 months | 7 months | 11 weeks | 5 months | 4 months | 7 months | 7 months | 6 months | <1yr | <1yr | <1yr |
| Severe developmental delay | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Profound intellectual disability | Yes | ** | ** | ** | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Acquired microcephaly | Yes | Yes | - | Yes | Yes | No | Yes | No | No | - | - |
| Facial dysmorphisms | Yes | Yes | - | - | - | - | - | - | - | - | - |
| Visual impairment | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | No | Yes | - |
| Retinal dystrophy | No | No | - | Normal ERG, Abnormal VEP | - | Abnormal ERG, Abnormal VEP | Abnormal ERG, Abnormal VEP | Abnormal ERG | - | - | - |
| Hearing impairment | Yes | Yes | - | - | - | - | - | - | - | - | - |
| Severe speech delay | Yes | Yes | - | - | Yes | Yes | Yes | - | - | - | - |
| Central hypotonia | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | - | - | - |
| Peripheral hypertonia | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | - | - | - |
| Poor head control | Yes | Yes | Yes | Yes | Yes | Yes | Yes | - | Yes | Yes | Yes |
| Ataxia | Yes | Yes | - | - | - | - | - | - | Yes | - | Yes |
| Dystonia | Yes | Yes | - | - | Yes | Yes | Yes | Yes | - | - | - |
| Spasticity | Yes | - | - | - | - | Yes | Yes | - | - | - | - |
| Cerebral palsy | Yes | Yes | - | - | - | - | - | - | - | - | - |
| Severe scoliosis | Yesd | No | - | - | - | Yes | Yes | - | - | - | - |
| Diffuse osteopenia | Yes | Yes | - | - | - | - | - | - | - | - | - |
| Deformity of the hip | Yes | Yes | - | - | - | Yes | Yes | - | - | - | - |
| Feeding difficulties | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | - | - | - |
| Aspiration | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | - | - | - |
a
Mutations are homozygous/biallelic in all patients.
b
Mutations were confirmed by Sanger Sequencing in all patients except patient 3. Variant in this patient is presumed, not confirmed as patient died before DNA was obtained.
c
Variant on protein level is p.Thr266_Phe271delinsLeuPhePhePheThrIleCysGlyMetThrSerCysIle.
d
One of the unaffected siblings also has severe scoliosis.
“-“ indicates no information available
**
indicates likely, but not formally tested.