Gene of the Month – September: LMNB1
LMNB1 is a gene that plays an important role in maintaining nuclear envelope stability and in regulating gene expression and is thereby also involved in nervous system development, among other processes. An international study published in the American Journal of Human Genetics now reports on de novo mutations in LMNB1 as the cause of severe microcephaly. The authors of the study identified three missense LMNB1 mutations in patients with pronounced primary microcephaly associated with relative short stature, intellectual disability and neurological features as the core symptoms. At a functional level, their experiments showed that the identified variants cause several structural changes in the nuclear lamina and revealed for example an increased frequency of mishappen or condensed nuclei.
Lamin B, the protein encoded by LMNB1, forms an important component of the nuclear lamina. This lamina is a network of structural proteins lining the inner surface of the nuclear membrane. It contributes to nuclear stability, which must be maintained to enable fundamental processes such as DNA replication, transcription or chromatin organization. LMNB1 variants have previously been associated with autosomal dominant leukodystrophy, a human disorder similar to multiple sclerosis.
Cristofoli F, Moss T, Moore HW, …, Van Esch H. De Novo Variants in LMNB1 Cause Pronounced Syndromic Microcephaly and Disruption of Nuclear Envelope Integrity. Am J Hum Genet. 2020 Sep 1:S0002-9297(20)30284-6. doi: 10.1016/j.ajhg.2020.08.015. Online ahead of print.