Table 2 Overview of all NAA10 variants with phenotype and functional data

From: A novel NAA10 variant with impaired acetyltransferase activity causes developmental delay, intellectual disability, and hypertrophic cardiomyopathy

Variant no. 1 2 3 4 5 6 7 8 9
This study Casey et al. [24] Popp et al. [25], Saunier et al. [26] Saunier et al. [26] Saunier et al. [26] Saunier et al. [26], Sidhu et al. [27] Popp et al. [25], Saunier et al. [26] Rope et al. [21], Myklebust et al. [23] Esmailpour et al. [28], Forrester et al. [29]
NAA10 variant (NM_003491.3) c.215T>C p.(Ile72Thr) c.128A>C p.(Tyr43Ser) c.319G>T p.(Val107Phe) c.384T>A p.(Phe128Ile) c.382T>A p.(Phe128Leu) c.247C>T p.(Arg83Cys) c.346C>T p.(Arg116Trp) c.109T>C p.(Ser37Pro) c.471+2T>A (p.Glu157fs45*)
Patients Male (3/3) Male (2/2) Female (1/1) Female (1/1) Female (2/2) Female (8/9) Male (1/9) Female (1/2) Male (1/2), Male (8/8) Male (4/4)
Inheritance Inherited Inherited De novo De novo De novo De novo/MGM De novo Inherited Inherited
Age of last examination (age of death) 3y 3mo–8y 6mo 20y–25y 8y 2mo 6y 5mo 17mo–8y 6mo 2y 2mo–14y (male patient died 1 week old) 5y 11mo–8y 1mo 5–16mo (5–16 mo) 14y–28y
X-inactivation Random Random Random (1/2), NA (1/2) Random (1/8), 82% (1/8), 100% (1/8), NA (5/8) Random
Female carriers No reported phenotypes Mild ID, cardiac arrhythmias and long QT, down slanting PF, VT, premature CAD, dysmorphic facial features, random XCI No reported phenotypes, >90% X-inactivation Toe syndactyly, short terminal phalanges
Patient phenotype
 DD/ID Yes Mild (1/2) moderate (1/2) Severe Yes Profound (1/2) severe (1/2) Severe (6/9), moderate (1/9), yes (1/9), NA (1/9) Severe (1/2) moderate (1/2) Severe Severe (3/4), mild (1/4)
 Growth failure No Yes (1/2) Yes Yes Yes (1/2) Yes (6/9), No (2/9), NA (1/9) Yes (1/2) Yes Yes
 Neurological Thin CC (1/3), relative paucity of frontal lobe (1/3), mild PVL (1/3), medulloblastoma (1/3) Hypo, mild dilation of LV, mild CA, seizures (1/2), prominent SF (1/2) Axial hypo/periph hyper, thin cc, borderline normal ventricles Axial Hypo/periph hyper, superventricular cyst without hydrocephaly Axial Hypo/ periph hyper (1/2), severe hypo (1/2), thin CC, parenchymal atrophy, seizures /infantile spasms Hypo (7/9), hyper (2/9), WMVL (2/9), thin CC (1/9), VM (1/9), PVL and HIE (1/9) Axial hypo/ periph hyper, enlarged ventricles, reduced periventricular volume, thin CC. Truncal hypo (4/8), CA or immature CC (3/8), enlarged ventricles (2/8) Hypo, bilateral anopthalmia/micropthalmia, seizures (2/4), ASCVD (1/4)
 Organs Hypertrophic cardiomyopathy, inguinal hernia (1/3) Cardiac arrhythmias, long QT, innocent HM, inguinal hernia, VT (1/2) PAS, ASD, long QT IRBBB Mild left ventricular diastolic dysfunction (1/2) PAS (1/9), PFO vs. ASD (1/9), long QT (1/9), SVT (1/9), pulmonary hyper (1/9), VH (2/9), IRBBB (1/9) IRBBB (1/2) Cardiac anomalies (VSD, PAS) (6/8) cardiac arrhythmias (5/8), inguinal hernia (3/8) Right VH (1/4)
 Skeletal Delayed closure of anterior fontanelle (1/3), barrel chest (1/3), high-arched palate (1/3) Scoliosis, small hands/feet, BAD, Toe syndactyly (1/2) Delayed closure of fontanels, large fontanels, delayed bone age, broad great toes, mild pectus carinatum Large fontanels (4/9), small feet/hands (2/9), clinodactyly (1/9), pectus exavatum (3/9), broad great toes (1/9) Small feet/hands (1/2), high-arched palate (1/2), wide interdental spaces (1/2) Scoliosis, large fontanels (5/8), broad or widely spaced toes (2/8), delayed osseous development (1/8) High-arched palate, clinodactyly or syndactyly, scoliosis (3/4), pectus exavatum (3/4), pes planus (2/4)
 Other Minor unspecific dysmorphic facial features (1/3) Prominent dysmorphic facial features Minor unspecific dysmorphic facial features Minor unspecific dysmorphic facial features Minor unspecific dysmorphic facial features Minor unspecific dysmorphic facial features, autism spectrum disorder Minor unspecific dysmorphic facial features, hypoplastic scrotum Dysmorphic facial features, large ears (6/8), prominent eyes (4/8), cryptorchidism (5/8) Dysmorphic facial features, large abnormally formed ears and abnormally developed eyes
Functional studies
 Catalytic activity Reduced NAA10 activity, most likely intact NatA activity Reduced NAA10 activity Reduced NAA10 activity NA Reduced NAA10 activity Reduced NAA10 activity, most likely reduced NatA activity Reduced NAA10 activity Reduced NAA10 activity, reduced NatA activity NA
 Protein stability Reduced Reduced Most likely reduced NA Reduced No reduction in protein stability No reduction in protein stability No reduction in protein stability NA
 Other features Reduced NatA complex formation Loss of NAA10 expression
  1. This table lists main phenotypic features and main findings from functional studies only. For a full overview of patient phenotypes and results from functional studies for each variant, please see respective references.
  2. ASCVD, arteriosclerotic vascular disease; ASD, atrial septal defect; BAD, bilateral acetabular dysplasia; CA, cerebral atrophy; CAD; coronary artery disease; CC, corpus calossum; DD, development delay; HIE, hypoxic-ischemic encephalopathy; HM, heart murmur; hyper, hypertonia; hypo, hypotonia; ID, intellectual disabilities; IRBBB, Incomplete right bundle branch block; LV, lateral ventricles; MGM, maternal germ line mosaicism; mo, months; NA, not available; PAS, Pulmonary artery stenosis; periph, peripheral; PF, palpebral fissures; PFO, Patent Foramen Ovale; PVL, periventricular leukomalacia; SF, sylvian fissures; SVT, superventricular tachycardia; VH, ventricular hypertrophy; VM, ventriculomegaly; VT, ventricular tachycardia; WMVL, white matter volume loss; XCI, X-chromosome inactivation; y, years.