Table 1.
Clinical features of GNB5-patients reported so far.
| Lodder et al., 2016 Family A II.1 | Lodder et al., 2016 Family A II.2 | Lodder et al., 2016 Family B II.1 | Lodder et al., 2016 Family C II.2 | Lodder et al., 2016 Family C II.3 | Lodder et al., 2016 Family D II.2 | Lodder et al., 2016 Family E II.1 | Lodder et al., 2016 Family E II.2 | Lodder et al., 2016 Family F II.1 | |
|---|---|---|---|---|---|---|---|---|---|
| Paternal allele | c.249G > A p.Asp84Valfs∗52 | c.249G > A p.Asp84Valfs∗52 | c.249+1G > T p.Asp84Leufs∗31 | c.249+3A > G p.Asp84Valfs∗31 | c.249+3A > G p.Asp84Valfs∗31 | c.906C > G p.Tyr302∗ | c.242C > T p.Ser81Leu | c.242C > T p.Ser81Leu | c.242C > T p.Ser81Leu |
| Maternal allele | c.994C > T p.Arg332∗ | c.994C > T p.Arg332∗ | c.249+1G > T p.Asp84Leufs∗31 | c.249+3A > G p.Asp84Valfs∗31 | c.249+3A > G p.Asp84Valfs∗31 | c.906C > G p.Tyr302∗ | c.242C > T p.Ser81Leu | c.242C > T p.Ser81Leu | c.242C > T p.Ser81Leu |
| Gender, age (years) | F, 24 | F, 22 | F, 8 | F, 13 | M, 11 | F, 14 | F, 15 | M, 10 | M, 25 |
| Birth weight (percentile) | 3,580 g (50th) | NA | 2,980 g (15th) | 2,751 g (15th) | NA | 2,845 g (15th) | NA | NA | NA |
| Ethnicity | Italy | Italy | Jordan | Puerto Rico | Puerto Rico | India | Morocco | Morocco | Brazil |
| Consanguinity | - | - | + | + | + | - | - | - | + |
| Verbal understanding | NA | NA | nonverbal | unremarkable | unremarkable | NA | NA | NA | NA |
| Speech Development | + | + | nonverbal | nonverbal | delayed | nonverbal | + | + | NA |
| Intellectual disability (ID) | Severe ID | Severe ID | Severe ID | Severe ID | Global developmental delay | Severe ID | Mild ID | Mild ID | Mild ID |
| Epilepsy | + | + | + | - | - | + | - | - | - |
| Retinal Disease | NA | Retinal degeneration | NA | NA | NA | NA | NA | NA | Keratoconus |
| Nystagmus | + | + | + | + | + | + | NA | - | NA |
| Sinus sick syndrome | + | Bradyarrhythmia | + | + | + | increased PR interval/ | + | + | + |
| (intermittent Wenckebach) | |||||||||
| Minimum heart rate (bpm) | 24 | 39 | NA | paced | paced | NA | 20 | 16 | |
| Maximum heart rate (bpm) | 163 | 192 | NA | paced (27% heartbeats on Holter) | paced (20% heartbeats on Holter) | NA | 176 | 180 | NA |
| Chronotropic response | NA | NA | NA | + | + | NA | unremarkable | unremarkable | NA |
| Escape beats | + | + | NA | paced | paced | NA | + | + | NA |
| Pacemaker implantation | - | - | - | + | + | - | - | + | NA |
| Cardiac anomalies | - | PFO | NA | - | - | - | - | - | NA |
| Hypotonia | + | + | + | + | + | + | - | impaired fine motor skills | - |
| Gastroesophageal Reflux | + | + | - | + | + | + | - | - | NA |
| Others | Abnormally mitochondrial shape, focal z-band streaming and type1 fiber predominance | ||||||||
| Dysmorphic feature(s) | |||||||||
| Paternal allele | c.242C > T p.Ser81Leu | c.242C > T p.Ser81Leu | c.242C > T p.Ser81Leu | c.242C > T p.Ser81Leu | c.242C > T p.Ser81Leu | c.355delG p.Ala119Profs∗16 | c.355delG p.Ala119Profs∗16 | c.737G > A p.Arg246Gln | c.222_226delTAAGA p.Asp74Glufs∗52 |
| Maternal allele | c.242C > T p.Ser81Leu | c.242C > T p.Ser81Leu | c.242C > T p.Ser81Leu | c.242C > T p.Ser81Leu | c.242C > T p.Ser81Leu | c.355delG p.Ala119Profs∗16 | c.355delG p.Ala119Profs∗16 | c.222_226delTAAGA p.Asp74Glufs∗52 | c.242C > T p.Ser81Leu |
| Gender, age (years) | F, 12 | F, 11 | F, 5 | F, 7 | F, 11 | M, 3 | F, 11 | M, 2 | F, 2.5 |
| Birth weight (percentile) | 50th centile | 50th centile | NA | 50th centile | NA | NA | 1800 g ( < 1st) | 3311 g (50th) | 1698 g ( < 1st) (Intrauterine growth restricted) |
| Ethnicity | Saudi | Saudi | Saudi | Saudi | Saudi | NA | NA | European/Caucasian | European/Caucasian |
| Consanguinity | + | + | + | - | - | + | + | - | - |
| Verbal understanding | + | + | + | + | + | “no developmental milestones” | “no developmental milestones” | nonverbal | + |
| Speech Development | Severe language delay | Severe language delay | Severe language delay | Severe language delay | Severe language delay | “no developmental milestones” | “no developmental milestones” | nonverbal | expressive speech delay |
| Intellectual disability (ID) | Normal IQ, but school performance issues | Normal cognitive development | NA | Normal IQ | NA | Severe ID | Severe ID | Severe ID | Mild ID |
| Epilepsy | NA | NA | NA | NA | NA | + | + | - | - |
| Retinal Disease | NA | NA | NA | NA | NA | Retinal degeneration | Retinal degeneration | Severe reduction in cone and rode function | - |
| Nystagmus | NA | NA | NA | NA | NA | + | + | + | Strabismus |
| Sinus sick syndrome | NA | NA | NA | NA | NA | Sinus arrhythmia/ Sinus bradycardia | Sinus arrhythmia/ Sinus bradycardia | Sinus arrhythmia/ Sinus bradycardia | + |
| Minimum heart rate (bpm) | NA | NA | NA | NA | NA | NA | NA | 71 | 36 |
| Maximum heart rate (bpm) | NA | NA | NA | NA | NA | NA | NA | 183 | 176 |
| Chronotropic response | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Escape beats | NA | NA | NA | NA | NA | NA | NA | + (prior to pacing) | + |
| Pacemaker implantation | NA | NA | NA | NA | NA | Refused by parents | Refused by parents | + | + |
| Cardiac anomalies | NA | NA | NA | NA | NA | - | - | - | - |
| Hypotonia | - | - | NA | + | NA | + | + | + | + |
| Gastroesophageal Reflux | NA | NA | NA | NA | NA | normal (abdominal US examination) | normal (abdominal US examination) | + | - |
| Others | ADHD, Hyperactivity | Inattentive type ADHD | Motor delay | Motor delay | ADHD, mild motor delay | autistic (midline hand automatism, no eye contact) | autistic (midline hand automatism, no eye contact) | center-sided hearing loss, hypertonia, upper extremity jerking motions, laryngomalacia hypertonia | tympanostomy tubes |
| Dysmorphic feature(s) | prominent forehead, micro-brachycephaly (acquired) | prominent forehead, micro-brachycephaly (acquired) | thin corpus callosum (brain MRI) | ||||||
M, male: F, female; NA, not available; +, clinical trait present; -, clinical trait not present; bpm, beats per minute; ADHD, attention deficit hyperactivity disorder; PFO, patent foramen ovale; US, ultrasound.