PR 2 (Hiraide et al 4) | Individual 4 | Individual 2 | PR 1 (Hiraide et al 3) | PR 2 (Hiraide et al 3) | Individual 3 | Individual 1 | (Den et al 5) | |
Source | NA | INSERM (Nantes) | CAUSES G272 | NA | NA | Blueprint Genetics | CAUSES G482 | NA |
Variant | c.386T>G: p.(Val129Gly) | c.2932C>T: p.(Gln978Ter) | c.3964C>T: p.(Gln1322Ter) | c.5524C>T: p.(Arg1885Trp) | c.5575C>T: p.(Arg1902Cys) | c.5833T>P: p.(Phe1945Leu) | c.5589+1G>A:(p.?) | c.5644_5647del:p.(Ile1882Serfs*118) |
Class of variant | Missense | Nonsense | Nonsense | Missense | Missense | Missense | Possible splicing | Frameshift |
Inheritance | De novo | De novo | De novo | De novo | De novo | De novo | De novo | De novo |
Additional gene variants of relevance | None | None | +* | None | +* | None | None | None |
Age at last follow-up (years) | 7 | 12 | 19 | 10 | 34 | 3.5 | 10 | NA |
Sex | Male | Male | Female | Female | Male | Male | Male | Female |
Growth | ||||||||
Weight (birth, SD) | 3008 g (+0.82) | 3930 g (+1.13) | NA | 3550 g (+1.4) | 3600 g (+1.5) | 3062 g (−0.60) | 3402 g (+0.11) | 2750 g (−1.6) |
Head circumference (birth, SD) | NA | 34.5 cm (+0.03) | NA | 34.5 cm (+1.1) | NA | NA | NA | 34 cm (−0.1) |
Length (birth, SD) | 50 cm (+1.4) | 53 cm (+1.65) | NA | NA | NA | NA | NA | 45.2 cm (−2.6) |
Height (last follow-up, SD) | 124.6 cm (−0.23) | 147 cm (−0.29) | 172 cm (+1.4) | 143 cm (+0.8) | 176 cm (+0.6) | 104 cm (+1.0) | 146 cm (+0.5) | NA |
Weight (last follow-up, SD) | 28.8 kg (+0.49) | 70 kg (+2.51) | 66 kg (+0.9) | 52 kg (+2.6) | 92 kg (+1.5) | 16.6 kg (+0.6) | 33 kg (−0.2) | NA |
Head circumference (last follow-up, SD) | 54.5 cm (+1.4) | 54 cm (+0.14)† | 55 cm (+0.63)† | NA | 55 cm (−0.07)† | 48.0 cm (−1.3) | NA | NA |
Development | ||||||||
Speech impairment | + | + | + | − | NA | + | + | + |
Developmental delay | Motor development normal | + | + | + | + | + | + | + |
Intellectual disability | + (IQ 56–64) | + | + Mild | + (TK-Binet IQ 64) | + (TK-Binet IQ 10) | + | + | + |
Neurology | ||||||||
Seizures | + | + | + | + | + | + | + | + |
Age of onset (years) | 3.6 | 2.5 | 12 | 2.75 | 3.9 | 3.5 | 2.5 | 1.9 |
Multiple seizure types | Myoclonic absence seizures only | + | + | + | + | + | + Moderate, with ADHD | − |
EEG abnormalities | + | NA | + | + | + | + | + | + |
Findings on brain imaging (modality) | − (MRI) | − (MRI) | − (MRI) | − (MRI) | − (MRI) | + (MRI) | + (MRI) | + |
Autism | + | − | + | + | + | + | − | + |
+ indicates a positive finding, − indicates the documented absence of a finding, and NA refers to results that were not documented or are not available.
Variants are numbered with reference to National Center for Biotechnology Information (NCBI) accession number NM_001353345.1.
†SD for head circumferences in children older than 17 years is unavailable so SD values for 17 years are used. All other anthropometric centiles are based on WHO growth charts.
**Individual 2 had a variant in CHRNA7 and inherited variants in LRPPRC, GLI2, TUBB2 and PTCH1. PR 2 had variants in KCNH7 and CNKSR2.3
ADHD, attention deficit hyperactivity disorder; CAUSES, Clinical Assessment of the Utility of Sequencing and Evaluation as a Service.