Table 2.
Summary of cases with a pathogenic or likely pathogenic mosaic variant in a proband or parental sample
| Case | Proband gender/age | Clinical phenotype | Gene | Zygosity/VAF | Chromosome (hg19) | HGVS DNA and protein reference | Variant type/predicted effect | Parent of origin/VAF | Relevant disease association | Supporting references |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Male/6 mo | Failure to thrive, profound hypotonia, global developmental delay, microcephalic, bilateral esotropia, short palpebral fissures, protuberant tongue, sparse scalp hair, hypsarrhythmia by long-term electroencephalographic monitoring, delayed myelination on MRI | ARX | Mosaic (12%) | Chr X:25025232 C > T | NM_139058.2 c.1444G > A p.(Gly482Ser) | Substitution/missense | De novo | (XL) Early infantile epileptic encephalopathy 1 | Shoubridge et al. 2012; Shoubridge et al. 2010; Gronskov et al. 2014; Poirier et al. 2005 |
| 2 | Male/11 yr | Generalized epilepsy, global developmental delay, intellectual disability, autism, attention deficit hyperactivity disorder, able to walk independently with orthotics and verbally communicate | CDKL5 | Mosaic (17%) | Chr X:18602452 G > A | NM_003159.2 c.533G > A p.(Arg178Gln) | Substitution/missense | De novo | (XL) Early infantile epileptic encephalopathy 2 | Bahi-Buisson et al. 2012; Kilstrup-Nielsen et al. 2012; Mei et al. 2014; Masliah-Plachon et al. 2010; Stosser et al. 2018; Kothur et al. 2018; Olson et al. 2019 |
| 3 | Male/1 yr | Global developmental delay, seizures, chorea, hypotonia, short stature, poor feeding, ptosis, frontal bossing, micrognathia | TRIP12 | Mosaic (12%) | Chr 2:230679862 G > A | NM_004238.2 c.1540C > T p.(Arg514Ter) | Substitution/nonsense | De novo | (AD) Clark–Baraitser syndrome | Bramswig et al. 2017a; Zhang et al. 2017; Louie et al. 2020 |
| 4 | Male/7 yr | Localization-related partial epilepsy with complex partial seizures, nonambulatory, global developmental delay, postnatal growth retardation, intellectual disability, autism, hyperopia, chronic constipation, dysphagia | IQSEC2 | Hemi (98%) | Chr X:53264051 G > A | NM_001111125.2 c.3817C > T p.(Gln1273Ter) | Substitution/nonsense | Mosaic mother (11%) | (XL) Mental retardation 1 | Barrie et al. 2019a; Ewans et al. 2017; Radley et al. 2019; Mignot et al. 2019 |
| 5 | Female/8 yr | Global developmental delay, fine motor delay, hirsutism, agenesis of the corpus callosum, hypotonia, tethered spinal cord, exotropia, clubfoot, tall forehead, downslanting palpebral fissures, macrostomia | ARID1A | Mosaic (19%) | Chr 1:27092947 G > A | NM_139135.2 c.2879-1G > A p.? | Substitution/splicing | De novo | (AD) Coffin–Siris syndrome 2 | Tsurusaki et al. 2012; Santen et al. 2013; Wieczorek et al. 2013 |
| 6 | Male/7 yr | Periventricular white matter changes on MRI, mild intellectual disability, global developmental delay, hypotonia, GERD, myopathic facies, thickened low-set ears, flared nasal alae, upturned nasal tip | ARID2 | Het (46%) | Chr 12: 46245833_46245834delAG | NM_152641.3 c.3927_3928delAG p.(Gly1310Glufs Ter5) | Deletion/frameshift | Mosaic mother (4%) | (AD) Coffin–Siris syndrome 6 | Tsurusaki et al. 2012; Bramswig et al. 2017b; Bogershausen and Wollnik 2018 |
| 7 | Female/2 yr | Macrocephaly, hirsutism, global developmental delay, bilateral perisylvian polymicrogyria with mildly enlarged ventricles on MRI | PIK3R2 | Mosaic (18%) | Chr 19:18273784G > A | NM_005027.3 c.1117G > A p.(Gly373Arg) | Substitution/missense | De novo | (AD) Megalencephaly- polymicrogyria-polydactyly- hydrocephalus syndrome 1 | Mirzaa et al. 2015; Riviere et al. 2012; Madsen et al. 2018 |
(VAF) Variant allele frequency/fraction, (hemi) hemizygous, (het) heterozygous, (N/A) not applicable, (XL) X-linked, (AD) autosomal dominant, (MRI) magnetic resonance imaging, (GERD) gastroesophageal reflux disease.
aCase previously reported.