How an altered protein and fussy neurons conspire to cause microcephaly

Sub: Science and tech

Sec: Health in news

Microcephaly:

Microcephaly is a condition where a baby’s head and brain are significantly smaller than normal.
Symptoms include poor motor function, speech, abnormal facial features, and intellectual disability.
The condition originates during the embryo’s peak brain development phase due to abnormal cell division.
Diagnostic Methods: Clinicians diagnose microcephaly before birth using fetal ultrasound and magnetic resonance imaging (MRI).

Role of the SASS6 Gene:

Since 2014, the SASS6 gene and its variants have been linked to microcephaly.
Researchers at Nantong University, China, found that one functional copy of the SASS6 gene retains some function, while both non-functional copies lead to embryo death.
Findings confirm SASS6’s crucial role in microcephaly and expand the understanding of its mutation spectrum.
Recent Studies and Findings:
- Six more SASS6 gene variants have been identified since the March study.
- Researchers continue to explore the implications of these variants and their impact on cell division and development.
- In February 2024, University of Cologne researchers showed that cells without functional SASS6 genes could make abnormal centrioles but failed to develop into neurons.

Impact of Consanguinity:

Consanguinity, or marriages between closely related individuals, significantly increases the risk of congenital microcephaly.
Microcephaly can result from mutations in 30 genes, 10 of which are crucial for centriole assembly and function during cell division.

The Ile62Thr Mutation:

The SASS6 gene, discovered in C. elegans in 2004, encodes a protein essential for centriole assembly.
In 2014, researchers identified the Ile62Thr mutation in the SASS6 gene in a consanguineous Pakistani family with microcephaly.
The Ile62Thr mutation impairs centriole function, causing microcephaly but allowing survival into adulthood. When combined with another centriolar protein mutation, it increases replication failure and embryo death.

Variability in Cell Tolerance:

Different cell types have varying tolerances for centriole defects. Neuron precursor cells are particularly sensitive.
This sensitivity leads to brain and head deficits and intellectual disability in individuals with defective SASS6 genes.

Source: TH