Variants in LMNB1 Cause Syndromic Microcephaly, Study Suggests

Jan, 2021 - By WMR

According to a new collaborative research study by the researchers of Greenwood Genetic Center (GGC) and international group of scientists from Spain, Italy and Belgium have reported to confirm that variants in LMNB1 are responsible for syndromic microcephaly with symptoms including intellectual disability variable short stature, and other neurological symptoms. The study involved seven patients from five families comprising novel de novo variants in LMNB1, exhibiting pronounced primary microcephaly as the essential feature. Moreover, these variants were recognized by utilizing exome sequencing.

In addition, researchers reported that functional analysis of each of the gene variants and resultant lamin B1 protein exhibited that that these variants function dominantly to dislocate nuclear envelope integrity that further propels the nucleus to become distorted.

Tonya Moss, co-lead author stated, "We used a HeLa cell system to analyze the three missense mutations in this gene and demonstrated impaired function of the nuclear lamina. Two other variants displayed misshapen nuclei and a decrease in nuclear localization of the lamin B1 protein, and another showed an increased frequency of condensed nuclei.â€

Researchers also explained that as this gene variant encompasses multiple domains, hence different variants in LMNB1 are more likely to function by utilizing different mechanisms, requiring a case-by-case analysis of pathogenicity that can aid in the future treatment studies along with reproductive planning for families.