LINS1 gene
LINS1 gene is located on chromosome 15q26.3 spanning 35.26 Kb sequence. It consists of seven exons.
Types of mutations and pathophysiologic mechanism
All types of variants including missense, nonsense, and frameshift variants have been reported until date in the gene.
The following table shows the different variants reported in the LINS1 gene
The LINS1 gene encodes a 757 amino acid long polypeptide comprising of two ‘lines' homology domains LINES_N (194-542) and LINES_C (712-747). The LINS1 product is expressed in various tissues, including adult testis, prostate, spleen, thymus, skeletal muscle, fetal kidney, and brain. There is a limited information on the physiological function of LINS1 in human development. LINS1 gene is homologous to the Lines gene in Drosophila. Studies on Lines gene has shown its involvement in tissue and stage-specific Wnt signalling events in the cell-fate specification. This suggests that the human LINS1 protein might also be involved in the WNT signalling pathway.
WNT signalling is essential for embryonic development in all animals. WNT signaling pathway also plays an essential role in regulating neuronal connectivity in the nervous system. Aberrant WNT signaling pathway has been associated with ID and psychiatric disorders such as autism, bipolar disorder, and schizophrenia.
Diagnostic testing
A diagnosis of Intellectual developmental disorder, autosomal recessive 27 is made, based on clinical findings and presence of biallelic pathogenic variants in the LINS1 gene.
Molecular genetic testing is used to identify variant in the LINS1 gene. This includes use of NGS-panel based multi-gene or whole-exome sequencing study. Exon5 seems to be the hotspot in LINS1 gene which can be used as a first line genetic test.
Multi-gene testing: In individuals presented with non-syndromic ID, multi-gene panel testing can aid to assess LINS1 and other genes of interests.
Whole-Exome sequencing: In individuals with a broad range of symptoms along with ID, exome sequencing is commonly used to identify the causative gene involved. This test investigates all the coding genes present.
LINS1