This report describes Hengel-Maroofian-Schols syndrome (HEMARS), a newly characterized syndromic neurodevelopmental disorder associated with the human BCAS3 gene; HEMARS exhibits autosomal recessive inheritance. BCAS3 encodes a large, highly conserved cytoskeletal protein with multiple inferred functions. There is a single orthologous gene in Drosophila, rudhira, for which multiple genetic reagents are available, including overexpression and RNAi targeting constructs, and alleles caused by insertional mutagenesis.
The human BCAS3 gene has not been introduced into flies.
Animals in which RNAi against rudhira in driven by an early-acting pan-neuronal driver die during the embryonic or larval/pupal stages (depending upon the strength of the RNAi reagent). Use of a motor-neuron specific driver results in lethality at larval/pupal stages. Using a later-acting pan-neuronal driver allows survival to adulthood; phenotypes observed include reduced longevity, severe locomotion defects and a wing phenotype.
[updated Jan. 2022 by FlyBase; FBrf0222196]
[HENGEL-MAROOFIAN-SCHOLS SYNDROME; HEMARS](https://omim.org/entry/619641)
[BCAS3 MICROTUBULE-ASSOCIATED CELL MIGRATION FACTOR; BCAS3](https://omim.org/entry/607470)
This disease is characterized by global developmental delay accompanied by pyramidal tract involvement, microcephaly, short stature, strabismus, dysmorphic facial features, and seizures (Hengel et al., 2021: pubmed:34022130; FBrf0249195).
Hengel-Maroofian-Schols syndrome (HEMARS) is an autosomal recessive neurodevelopmental disorder characterized by severe global developmental delay apparent from infancy or early childhood. Affected individuals have delayed walking or inability to walk, impaired intellectual development with poor or absent speech, pyramidal signs manifest as lower limb spasticity, poor overall growth often with short stature and microcephaly, and dysmorphic facial features. Some patients develop seizures. Brain imaging shows thinning of the posterior part of the corpus callosum, delayed myelination, and cerebral and cerebellar atrophy (Hengel et al., 2021; pubmed:34022130). [from MIM:619641; 2022.01.09]
In a study of 15 individuals from 8 unrelated families, germline bi-allelic loss-of-function variants of BCAS3 were observed to be associated with the disease (Hengel et al., 2021: pubmed:34022130; FBrf0249195).
Hengel-Maroofian-Schols syndrome (HEMARS) is caused by homozygous or compound heterozygous mutation in the BCAS3 gene. [from MIM:619641; 2022.01.09]
BCAS3 microtubule-associated cell migration factor (BCAS3) is a large, highly conserved cytoskeletal protein proposed to be critical in angiogenesis and implicated in human embryogenesis and tumorigenesis; recent work suggests a critical role in neural tissue development (Hengel et al., 2021: pubmed:34022130; FBrf0249195).
The BCAS3 protein participates in the regulation of cell polarity and directional endothelial cell migration by mediating both the activation and recruitment of CDC42 and the reorganization of the actin cytoskeleton at the cell leading edge; has also been shown to stimulate histone acetyltransferase activity and to bind to chromatin. [Gene Cards, BCAS3; 2021.06.14]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human BCAS3 (1 Drosophila to 1 human). Dmel\rudhira shares 32% identity and 44% similarity with the human gene.
