Table 1 Clinical features and variants found in the 13 individuals of the cohort.
Individual 1 | Individual 2 | Individual 3 | Individual 4 | Individual 5 | Individual 6 | Individual 7 | Individual 8 | Individual 9 | Individual 10 | Individual 11 | Individual 12 | Individual 13 | Total | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Age on follow-up | 6 years old | 10 years old | 14 years old | 11 years old | 5 years old | 3 months old | 9 years old | 11 years old | 10 years old | 13 years old | 11 years old | 32 years old | 10 years old | |
Gender | M | M | M | M | M | M | M | M | F | M | M | M | M | 9 M/1 F |
Motor delay | + | + | + | + | + | + | + | + | - | + | + | + | + | 12/13 |
Speech delay | + | + | + | + | - | + | + | + | + | + | + | + | + | 12/13 |
Degree of delay | Severe | Moderate | Severe | Severe | - | Mild | Severe | Mild | Severe | Mild | Severe | Mild | Severe | |
Behavioral problems | + | + | - | + | + | + | + | + | + | + | + | + | + | 12/13 |
Type of disorder | Psychomotor agitation | Autism spectrum disorders | Aggressivity, temper tantrums | Hyperactivity, aggressivity, obsessive compulsive behaviors | ADHD | Temper tantrums, anger bursts, severe psychomotor agitation, distractibility, attention disorders, enuresis, encopresis | Autism disorders, anxiety, aggressivity | Anxiety, attention disorders, | Autism spectrum disorder, hyperactivity | Attention disorder | Aggressive behavior, alcohol addiction | Oppositional defiant disorder, aggressivity, ADHD | ||
Intellectual disability (ID) | + | + | - | + | - | + | + | + | + | + | - | + | - | 10/13 |
Degree of ID | Moderate | Mild | Intellectual functions at the lower limit | Moderate | - | Mild | Moderate | Mild | Mild | Moderate | - | Mild | Mild | |
Neurological features | Cerebellar ataxia | - | Impaired fine motor skills, slight balance disorder, left laryngeal paralysis; limitation of abduction of the left eye with strabismus | - | Hypotonia | - | Impaired fine and gross motor skills, balance disorders, dysarthria | Impaired fine motor skills mild cerebellar ataxia, dysarthria | Action tremor | - | Impaired fine motor skills | - | - | 7/13 |
Neurosensory disorders | - | - | - | - | - | Hyperopia and high astigmatism | - | Hyperopia | Hyperopia, astigmatism | - | Astigmatism, hyperopia | Strabismus | Mild unilateral hearing impairment | 6/13 |
MRI findings | Thin corpus callosum | Mild myelination delay | Occipital meningocele, disrupted superior cerebellar vermis, bilateral asymmetrical nodular heterotopias | - | - | - | Pineal cyst, low-set cerebellar tonsils | Subcortical white matter T2 signal hyperintensity congruent with myelination delay | Subcortical white matter T2 signal hyperintensity congruent with myelination delay | UN | UN | UN | Type 1 Arnold–Chiari malformation | 6/13 |
Feature | Individual 1 | Individual 2 | Individual 3 | Individual 4 | Individual 5 | Individual 6 | Individual 7 | Individual 8 | Individual 9 | Individual 10 | Individual 11 | Individual 12 | Individual 13 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Dysmorphic features | Wide mouth, high forehead, low-set ears | Frontal bossing, triangular face, facial hypertrichosis, pointed frontal hairline, thick eyebrows, short philtrum, protruding incisor teeth, generalized hirsutism, long face, wide mouth, low-set large ears | - | - | - | UN | Hypotonic long face, wide mouth, large ears, bulbous nose tip | High forehead, large ears | High forehead, bulbous nose tip | Brachycephaly, long and thin fingers, plagiocephaly, low-set large ears | Long and thin fingers, large ears | Small and low-set ears, long and thin fingers | - | 8/13 |
Epilepsy | - | - | Focal motor seizures | Febrile seizures, generalized tonic–clonic seizures, atonic seizures, myoclonic and absence seizures; drug-resistant epilepsy | Generalized tonic–clonic seizures, febrile seizures, myoclonic, atonic; drug-resistant epilepsy | Generalized tonic–clonic | Generalized tonic–clonic seizures, febrile seizures, myoclonic, atonic | - | - | - | - | - | Absence seizures | 6/13 |
Exome sequencing strategy | Trio | Trio | Trio | Trio | Trio | Solo | Trio | Solo | Solo | Trio | Trio | Solo | Duo (mother) | |
GrCh37/Hg19 genomic variants | chr8:g.68170369C>T | chr8:g.68112696G>A | chr8:g.68139835T>C | chr8:g.68172127del | chr8:68169969 | chr8: 68152451 | chr8:g.68200211delT | chr8:g.68178422G>A | chr8:g.68178422G>A | chr8:g.68139728G>A | chr8:g.68139728G>A | chr8:g.68138302G>A | chr8:68170366G>A | |
cDNA variants | NM_006421.4:c.2392G>A | NM_006421.4:c.5320C>T | NM_006421.4:c.3592–2A>G | NM_006421.4:c.2158del | NM_006421: c.C2524T | NM_006421.4: c.2923_2924dup | NM_006421.4:c.1006delA | NM_006421.4:c.1942C>T | NM_006421.4:c.1942C>T | NM_006421.4:c.3697C>T | NM_006421.4:c.3697C>T | NM_006421.4:c.4033C>T | NM_006421.5c.2395C>T | |
Amino acid variants | p.(Asp798Asn) | p.(Arg1774*) | p.? | p.(Leu720Serfs*24) | p.(Gln842*) | p.(Cys976Phefs*6) | p.(Met336Trpfs*2) | p.(Gln648*) | p.(Gln648*) | p.(Gln1233*) | p.(Gln1233*) | p.(Arg1345*) | p.(Arg799*) | |
Familial segregation | De novo | De novo | De novo | De novo | De novo | De novo | Paternally inherited | Paternally inherited | Paternally inherited | Paternally inherited | Paternally inherited | UN | Not inherited from mother, paternal sample unavailable |
