Humans have two copies of DNA. Individuals with intellectual developmental disorder have a disease causing error (known as mutation/variant) present on both copies of the LINS1 gene. Consider the gene to be a sequence of letters that code for words. If there is, any change in the sequence of letters then there is a corresponding change is the sentence. Similarly, when there is a change in the LINS1 gene, subsequently there will be its effect on the produced protein.
LINS1 protein is an important protein in the WNT signalling pathway. This pathway helps in the proper functioning of different proteins, cells and formation of organ systems particularly the nervous system. Thus, defective LINS1 protein can disrupt this pathway resulting in improper development of organ systems, more importantly nervous system and brain and can lead to clinical consequences.
How to confirm the diagnosis of Intellectual developmental disorder, autosomal recessive 27?
It is important to find out the location and the type of error in the LINS1 gene to confirm the diagnosis. For this purpose, there are different genetic tests available including multi-gene panel testing and Exome sequencing study.
Individuals who present with intellectual disability, as the main clinical feature and no other major abnormalities, a multi-panel gene testing or Exome sequencing is the choice as multiple genes along with LINS1 can be tested to identify the cause.
What is the risk in siblings of affected patients?
The mode of inheritance is autosomal recessive. Thus, parents of an affected child are presumed to be heterozygous (carrier) for the variant in the LINS1 gene. Hence, molecular testing is recommended in the parents to confirm the heterozygous status. If parental carrier status is confirmed, each sib of the affected child has a 25% chance of being affected, 50% chance of being an asymptomatic heterozygote/carrier and 25% chance of inheriting neither of the pathogenic variants.
Heterozygotes or carriers are asymptomatic and do not develop any clinical manifestations of the disease.
LINS1