Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy.

ABSTRACT:

Purpose

Lamins are the major component of nuclear lamina, maintaining structural integrity of the nucleus. Lamin A/C variants are well established to cause a spectrum of disorders ranging from myopathies to progeria, termed laminopathies. Phenotypes resulting from variants in LMNB1 and LMNB2 have been much less clearly defined.

Methods

We investigated exome and genome sequencing from the Deciphering Developmental Disorders Study and the 100,000 Genomes Project to identify novel microcephaly genes.

Results

Starting from a cohort of patients with extreme microcephaly, 13 individuals with heterozygous variants in the two human B-type lamins were identified. Recurrent variants were established to be de novo in nine cases and shown to affect highly conserved residues withi

SUBMITTER: Parry DA 

PROVIDER: S-EPMC7862057 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature