This report describes lissencephaly 6 with microcephaly (LIS6), which is a subtype of lissencephaly; LIS6 exhibits autosomal recessive inheritance. The human gene implicated in this disease is KATNB1 (katanin regulatory subunit B1), the enzymatic subunit of the katanin microtubule-severing protein required for microtubule disassembly at the mitotic spindle. There is a single orthologous gene in Drosophila, kat80, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
The human KATNB1 gene has not been introduced into flies.
Loss of Dmel\kat80 effected by RNAi and targeted to neural progenitor cells in the developing larval brain results in significantly reduced brain size; neuroblasts exhibit supernumerary centrosomes and spindle abnormalities during mitosis, leading to cell cycle progression delays and reduced cell numbers; sensory and motor neurons exhibit dendritic arborization defects. A small number of genetic and physical interactions of Dmel\kat80 have been described; see below and in the kat80 gene report.
[updated Sep. 2017 by FlyBase; FBrf0222196]
Lissencephaly represents a term for a spectrum of severe and rare brain malformations that result in a significant simplification (pachygyria) or even total absence (agyria) of brain convolutions. Based on the physical structure of the brain, lissencephaly can be generally divided into two distinct pathological forms: type I or classical lissencephaly, and type II or cobblestone lissencephaly (http://www.news-medical.net/health/Lissencephaly-Types.aspx; 2017.07.16).
[LISSENCEPHALY 6 WITH MICROCEPHALY; LIS6](https://omim.org/entry/616212)
[KATANIN, p80 SUBUNIT, B1; KATNB1](https://omim.org/entry/602703)
Lissencephaly-6 is an autosomal recessive neurodevelopmental disorder characterized by severe microcephaly and developmental delay. [from MIM:616212; 2017.09.18]
Lissencephaly-6 with microcephaly (LIS6) is caused by homozygous mutation in the KATNB1 gene.[from MIM:616212; 2017.09.18]
Brain imaging shows variable malformations of cortical development, including lissencephaly, pachygyria, and hypoplasia of the corpus callosum (summary by Mishra-Gorur et al., 2014; pubmed:25521378). [from MIM:616212; 2017.09.18]
The microtubule-severing protein katanin is a heterodimer of a 60-kD enzymatic subunit, KATNA1, and an 80-kD subunit, KATNB1, that targets the enzyme to centrosomes (Hartman et al., 1998; pubmed:9568719). Microtubule disassembly at centrosomes is involved in mitotic spindle function. [from MIM:602703; 2017.09.18]
One to one: 1 human to 1 Drosophila.
Moderate-scoring ortholog of human KATNB1 (1 Drosophila to 1 human). Dmel\kat80 shares 27% identity and 41% similarity with the human gene.
