Table 2 The summary of genotype and clinical features of patients with PAK3 mutations
family ID/ reference | family 1(this study) | family 2 Bienvenu T et al., 2000 [9] | family 3 Rejeb I,et al., 2008 [16] | family 4 Muthusamy B, et al., 2017, [11] | family 5 Gedeon AK, et al., 2003 [19] | family 6 Magini Pet al, 2014 [10] | family 7 Allen KM, et al., 1998 [12] | family 8 | |
|---|---|---|---|---|---|---|---|---|---|
Proband | Younger brother | Al-Shamsi A et al., 2016, [18] | |||||||
NM_002578 | c.1112G > A | c.199C > T | c.276 + 4A > G | c.880G > A | c.1094C > A | c.1167G > T | c.1255C > T | c.1279 T > C | |
NP_002569 | p.Cys371Tyr | p.Arg67Cys | p.Gly92ValfsX35 | p.Val294Met | p.Ala365GLu | p.Lys389Asn | p.Arg419* | p.Tyr427His | |
Domain | KD | PBD/AID | PBD/AID | KD | KD | KD | KD | KD | |
Cases sex (Age) | 2 males (4y2m; 2y1m) | 6 males (NA) | 4 males (27y, 21y) | 3 males (7y, 3y, 25y) | 13 males (4y 3mo-69y) | 2 males (2y 9mo, 6y) | 4 males (NA) | 1 male | |
Inheritance | Maternal | Maternal | Maternal | Maternal | Maternal | Maternal | Maternal | NA | |
Clinical phenotype | |||||||||
Facial feature | + | + | – | + | + | + | + | NA | NA |
Head MRI/ circumference abnormal | LVE, WMD, CCA/ relative small | LVW, CCA/ relative small | NA/ NA | NA/microcephaly | NA/ microcephaly | NA/− | CCA, LVE, CeH/ microcephaly | NA/ microcephaly | NA/ macrocephaly |
EEG/Epilepsy | +/− | −/− | NA/− | - / - | NA/ - | NA/ -(1 patient +) | +/ + | NA/ - | NA/ NA |
Motor development delay | + | + | + | + | + | + | + | + | + |
Language development delay | + | + | + | + | + | + | + | + | + |
Behavior abnormal | HyA, Agg | – | NA | Agg, HyA, et al | ADHD; Agg | Agg & antisocial, et al | – | 1 patient, HyA, et al | NA |
Other abnormals | rash infancy and pigment loss spots in the forehead in both siblings, psoriasis in older brother | – | hypotonia | pes planus; hypogenitalism | – | Severe ichthyosis, pectus excavatum, camptodactyly and syndactyly; hypotonia | – | obesity | |
family ID | family 9 Hertecant J et al., 2017 [8] | Family 10 Iida A et al., 2019 [15] | family 11 Peippo M et al., 2007 [13] | family 12 Deciphering Developmental Disorders S, 2015 [2] | family 13 Deciphering Developmental Disorders S, 2015 [2] | family 14 McMichael G et al., 2015 [20] | family 15 Horvath GA et al., 2018 [14] | family 16 Cartwright A et al., 2017 [17] | |
NM_002578 | c.1279 T > C | c.1282 T > A | c.1337G > C | c.1340C > T | c.1454delC | c.1477C > T | c.1579A > G | ex.6-18del | |
NP_002569 | p.Tyr427His | p.Trp428Arg | p.Trp446Ser | p.Ser447Phe | p.Pro485Leufs*35 | p.Arg493Cys | p.Ser527Gly | / | |
Domain | KD | KD | KD | KD | KD | KD | KD | / | |
Cases sex (Age) | 2 males (4y) | 2 male (siblings) (7y, 1y) | 5 males (6y-46y) | 1 female (NA) | 1 male (NA) | 1 male (NA) | 1 male (17.5y) | 1 male (6y) | |
Inheritance | De novo | Maternal | Maternal | De novo | Maternal | NA | Maternal | De novo | |
Clinical phenotype | |||||||||
Facial feature | – | NA | + | + | NA | NA | NA | + | |
Head MRI/ circumference | −/ macrocephaly | CA and CCA/ microcephaly | 1 patient hydrocephalus; 2 patients microcephaly | CCA; microcephaly | NA/ NA | InVH/ NA | LVE, CCA, WMC/ - | NA/ relative small | |
EEG/Epilepsy | NA/ - | NA/ 1 patient + | 4 patients +/ 1 patients + | NA/ NA | NA/ NA | NA/ + | +/ + | NA/ NA | |
Motor development delay | + | + | + | + | + | + | + | + | |
Language development delay | + | + | + | NA | NA | + | + | + | |
Behavior abnormal | Likely ASD, temper tantrums | autistic stereotype movement | Agg, HyA, psychosis, et al | Stereotypic behavior | NA | NA | Agg, restless, self-injury | ASD | |
Other abnormals | hypotonia | Hypotonia | Asthma, respiratory infections; hypotonia, 3 mothers mild feature | Hypotonia, lower limb spasticity | eye movement abnormal | prematurely born; cerebral palsy | NA | myopia and astigmatism | |