Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy.
David A ParryCarol-Anne MartinPhilip GreeneJoseph A Marshnull nullMoira BlythHelen CoxDeirdre DonnellyLynn GreenhalghStephanie Greville-HeygateVictoria HarrisonKatherine LachlanCaoimhe McKennaAlan J QuigleyGillian ReaLisa RobertsonMohnish SuriAndrew P JacksonPublished in: Genetics in medicine : official journal of the American College of Medical Genetics (2020)
We identify dominant pathogenic variants in LMNB1 and LMNB2 as a genetic cause of primary microcephaly, implicating a major structural component of the nuclear envelope in its etiology and defining a new form of laminopathy. The distinct nature of this lamin B-associated phenotype highlights the strikingly different developmental requirements for lamin paralogs and suggests a novel mechanism for primary microcephaly warranting future investigation.