| Aspect | Key details (concise) | Evidence/source (include PMID/DOI and year) |
|---|---|---|
| Disease framing / synonyms | KATNB1-related cortical malformation is described as severe congenital microlissencephaly / lissencephaly 6 with combined microcephaly and lissencephaly-spectrum cortical malformation. | Hu et al., *Neuron* (2014), DOI: 10.1016/j.neuron.2014.12.017; Peluso et al., *Genes* (2021), DOI: 10.3390/genes12070962; Jin et al., *Sci Rep* (2017), DOI: 10.1038/srep39902 (pqac-00000002, pqac-00000006, pqac-00000005) |
| Inheritance | Reported as autosomal recessive; families include consanguineous pedigrees and affected individuals with homozygous or compound heterozygous variants; parental heterozygosity shown for c.1416+1del. | Hu et al., *Neuron* (2014), DOI: 10.1016/j.neuron.2014.12.017; Peluso et al., *Genes* (2021), DOI: 10.3390/genes12070962 (pqac-00000003, pqac-00000006, pqac-00000007) |
| Core clinical features | Severe congenital microcephaly, global developmental delay / psychomotor impairment, seizures, hypertonia (especially lower limbs in aggregated series), and variable absent speech / failure to achieve independent walking. | Hu et al., *Neuron* (2014), DOI: 10.1016/j.neuron.2014.12.017; Peluso et al., *Genes* (2021), DOI: 10.3390/genes12070962 (pqac-00000003, pqac-00000000) |
| Head-size severity | Microcephaly is characteristic; aggregated summary reported head circumference from about -1.63 to -5.9 SD at birth, with further decline in many patients; 8/14 reportedly fell below -6 SD. | Peluso et al., *Genes* (2021), DOI: 10.3390/genes12070962 (pqac-00000000) |
| Neuroimaging pattern | Reduced cortical size / brain volume with simplified gyral pattern, shallow sulci, posteriorly enlarged lateral ventricles, thinning or abnormalities of the corpus callosum; relative sparing of cerebellum, basal ganglia, thalamus, and brainstem in the original Neuron report. | Hu et al., *Neuron* (2014), DOI: 10.1016/j.neuron.2014.12.017 (pqac-00000002, pqac-00000003) |
| Additional imaging findings across reports | Pachygyria, polymicrogyria, simplified gyral pattern, periventricular or bilateral nodular heterotopia, posterior fossa anomalies; in one 2021 case, subarachnoid dilatation, abnormal gyration, slight hippocampal malrotation, subcortical heterotopia, and slightly thickened cortex. | Peluso et al., *Genes* (2021), DOI: 10.3390/genes12070962 (pqac-00000000, pqac-00000004) |
| Reported case counts | Hu et al. studied 3 families / 3 probands in detail; one family reportedly had 5 affected individuals. Peluso summarized prior literature as 13 subjects from 9 families, while some aggregated phenotype counts were tabulated over 14 cases (including the newly reported case). | Hu et al., *Neuron* (2014), DOI: 10.1016/j.neuron.2014.12.017; Peluso et al., *Genes* (2021), DOI: 10.3390/genes12070962 (pqac-00000002, pqac-00000003, pqac-00000000) |
| Example pathogenic variants from primary reports | Homozygous start-codon–abolishing variant; homozygous missense variant in a conserved WD40 repeat (glycine to tryptophan); homozygous splice-donor variant causing exon 6 skipping (dele6); homozygous splice-site variant NM_005886.3:c.1416+1del. | Hu et al., *Neuron* (2014), DOI: 10.1016/j.neuron.2014.12.017; Peluso et al., *Genes* (2021), DOI: 10.3390/genes12070962 (pqac-00000002, pqac-00000004) |
| Other reported variant examples in literature summary | Additional literature summary lists homozygous pathogenic variants including S535L, L540R, V45I, and frameshift V150Cfs*22, supporting loss-of-function / severe functional impairment. | Brown review summary citing Mishra-Gorur/Hu era literature (2017) (pqac-00000001, pqac-00000017) |
| Population rarity | The 2021 splice variant c.1416+1del was absent from gnomAD v2.1.1 and HGMD at time of report; the original 2014 variants were absent from matched control populations. | Peluso et al., *Genes* (2021), DOI: 10.3390/genes12070962; Hu et al., *Neuron* (2014), DOI: 10.1016/j.neuron.2014.12.017 (pqac-00000004, pqac-00000002) |
| KATNB1 molecular role | KATNB1 encodes the p80 regulatory B-subunit of the katanin microtubule-severing complex; it regulates localization/activity of the catalytic A-subunit and is important for corticogenesis. | Lynn et al., *Front Cell Dev Biol* (2021), DOI: 10.3389/fcell.2021.692040 (pqac-00000029, pqac-00000031, pqac-00000032) |
| Mechanistic theme: centriole / cilia control | KATNB1 loss causes excess centrioles, increased mother centrioles, supernumerary cilia / aberrant ciliogenesis, linking disease to centrosome-cilia homeostasis defects. | Hu et al., *Neuron* (2014), DOI: 10.1016/j.neuron.2014.12.017; Zaidi et al., *Cells* (2022), DOI: 10.3390/cells11182895 (pqac-00000014, pqac-00000015) |
| Mechanistic theme: spindle / mitotic defects | Patient-derived or depleted cells show defective proliferation, abnormal mitotic spindles, aster-formation defects, reduced spindle-pole microtubules, supernumerary centrosomes, and cytokinesis-related abnormalities. | Hu et al., *Neuron* (2014), DOI: 10.1016/j.neuron.2014.12.017; Jin et al., *Sci Rep* (2017), DOI: 10.1038/srep39902; Lynn methods summary (2023) (pqac-00000014, pqac-00000016, pqac-00000033) |
| Mechanistic theme: Hedgehog signaling | Katnb1-null cells show defective Hedgehog signaling with reduced GLI1 and Patched expression, supporting a cilia-dependent developmental signaling defect upstream of impaired corticogenesis. | Hu et al., *Neuron* (2014), DOI: 10.1016/j.neuron.2014.12.017; Lynn methods summary (2023) (pqac-00000014, pqac-00000027) |
| Mechanistic theme: neurogenesis / migration | Loss or depletion impairs neurogenesis, reduces neural progenitor proliferation, increases cell death in some models, and disrupts neuronal migration; disease pathogenesis is linked to abnormal asymmetrically dividing neural progenitors. | Hu et al., *Neuron* (2014), DOI: 10.1016/j.neuron.2014.12.017; Jin et al., *Sci Rep* (2017), DOI: 10.1038/srep39902; Zaidi et al., *Cells* (2022), DOI: 10.3390/cells11182895 (pqac-00000014, pqac-00000016, pqac-00000015) |
| Human stem-cell / organoid evidence | Findings were confirmed in patient-derived KATNB1-mutant iPSCs and brain organoids, supporting relevance of spindle/MT and migration defects to human cortical development. | Jin et al., *Sci Rep* (2017), DOI: 10.1038/srep39902 (pqac-00000005, pqac-00000016) |


*Table: This table concisely summarizes the clinical, genetic, imaging, and mechanistic evidence for KATNB1-related cortical malformation using only the provided evidence snippets. It is useful as a structured reference for a disease knowledge base entry on microlissencephaly / lissencephaly 6.*