The major components of the nuclear lamina are type V intermediate filament proteins grouped in two distinct classes, namely A- and B type lamins. In mammals, B-type lamins are encoded by two distinct genes (LMNB1 [MIM: 150340] and LMNB2 [MIM: 150341], and expressed in almost all known cell types beginning at earliest stages of development.
The mutations causing the microcephaly phenotype are heterozygous, and almost all of them arose de novo. To date, all mutations are missense mutations except one splice variant.
Functional characterization of several different missense variants demonstrated that these variants appear to disrupt the integrity of the nuclear envelope. It is hypothesized that the mutations act in a dominant-negative way.
Diagnosis/testing
Mutations in LMNB1 can be identified using molecular genetic testing, either directly by sequencing of the gene or by exome/genome sequencing.