Table 1.
Molecular and clinical characterization for seven individuals with biallelic variants in ZNF142
| Family A | Family B | Family C | Family D | ||||
|---|---|---|---|---|---|---|---|
| A-II-1 | A-II-2 | B-II-1 | C-IV-3 | C-IV-7 | C-IV-8 | D-II-2 | |
| Sex | female | female | female | female | female | female | female |
| Age at most recent examination | 35 years | 33 years | 8 years | 18 years | 13 years | 13 years | 10 years |
| Ethnicity | Slovakian | Slovakian | Turkish | Pakistani | Pakistani | Pakistani | European |
| Family history | positive | positive | negative | positive | positive | positive | negative |
| Nucleotide alteration (NM_001105537.2; inheritance) | c. 817_818delAA; c.1292delG; compound heterozygous | c. 817_818delAA; c.1292delG; compound heterozygous | c.3175C>T; homozygous | c.4183delC; 4185G>A; homozygous | c.4183delC; 4185G>A; homozygous | c.4183delC; 4185G>A; homozygous | c.3698G>T; c.4498C>T compound heterozygous |
| Protein alteration (NP_001099007.1) | p.Lys273Glufs*32; p.Cys431Leufs*11 | p.Lys273Glufs*32; p.Cys431Leufs*11 | p.Arg1059* | p.Leu1395* | p.Leu1395* | p.Leu1395* | p.Cys1233Phe; p.Arg1500Trp |
| Neurodevelopment and Function | |||||||
| Developmental milestones | sit: 10
months walk: 15 months |
sit: 12
months walk: 24 months |
sit: 4
years wheel chair bound |
sit: 6 months walk: 1 year | sit: 15
months walk: 18 months |
sit: 15
months walk: 18 months |
sit: 12
months walk:18 months |
| Cognition | severely Impaired (IQ 52) |
severely impaired (IQ 50) |
moderately impaired IQ: not available |
severely impaired WIAS-R/FSIQ (59) |
severely impaired WISC-R/FISQ (40) |
severely impaired not able to perform WISC-R |
low average verbal IQ (81) non-verbal IQ (82) and FSIQ (78) |
| Seizure(s) (Age at onset) |
− | at least once, Generalized tonic-clonic (1–2 years) |
Once, generalized tonic clonic (2 years) |
7–8 times, tonic clonic (4 months) |
2x / week, tonic clonic (13 days) |
7–8 times, tonic clonic (13 days) |
− |
| Speech | delayed: singular words at 5
years last examination: cerebellar dysarthria with hypernasality, restricted vocabulary |
delayed: first 2–3 word sentences
at 5 years last examination: spastic speech with severely impaired speech initiation, restricted vocabulary |
(no speech) no expressive language, verbal comprehension intact | delayed speech; unable to speak in full sentences | delayed speech; unable to speak in full sentences | receptive and expressive speech delayed | Childhood apraxia of speech |
| Movement disorder characteristics and other neurological features | |||||||
| Dystonia (age of onset) |
segmental (4 years) |
segmental (4 years) |
generalized (1 year) |
− | − | − | − |
| Dystonia site of onset | neck | neck | neck | NA | NA | NA | NA |
| Areas involved in dystonia (most recent examination) | face, neck, upper limbs | face, neck, upper limbs | face, neck, trunk, all 4 limbs | NA | NA | NA | NA |
| Tremor | + | + | − | − | + | + | − |
| Ataxia | + | + | + | − | + | − | − |
| Other neurological features (age of onset) |
− | − | trunk hypotonia, choreatic movements | − | − | − | increased tone and reflexes in lower
limbs (3 years) |
| Brain MRI | not performed | not performed | signal intensities | normal | not performed | not performed | mild thinning of the posterior aspect of the body of the corpus callosum with associated mild reduction in white matter volume |
| Other features | dolichocephaly | dolichocephaly | − | dolichocephaly | − | dolichocephaly | − |
FSIQ, Full scale Intelligence quotient; IQ, intelligence quotient; WIAS-R, Wechsler Intelligence Scale for Adults-Revised; WISC-R, Wechsler Intelligence Scale for Children-Revised; NA, not applicable; (+), yes; (−), no.