Redcliffe Identifies Six Novel Variants in ANK1 and SPTB Genes previously implicated in Hereditary Spherocytosis type 1 and 2 in Autosomal Dominant Inheritance Mode
Redcliffe Life Sciences’ Clinical Exome Sequencing identifies the genetic aetiology of Hereditary Spherocytosis-Hemolytic Disorder. The investigator initiated studies are clinical studies, designed and managed by non-pharmaceutical company researchers and can be very helpful by playing a key role in addressing the important health science questions such as discovering genetic aetiology, mode of action and molecular function-based treatment options. With the advent of Next Generation Sequencing (NGS) technology, identifying novel genetic variants in rare inherited disorders have improved remarkably.
Delhi based Redcliffe Life Sciences' “Clinical Exome Sequencing" looking at various clinically implicated genes at once to do research on the genome-wide association studies for specific genetic disorders.
Redcliffe Life Sciences’ Clinical Exome Sequencing test consists of more than 6000 genes. In this particular study performed on 10 individuals shares common clinical manifestations and shares family history. Out of these analysed 10 cases, five were male and five were female with age ranging from five months to 32 years. The analysed 10 patients had common features such as spherocytes, low haemoglobin, jaundice, splenomegaly, positive Epithelial membrane antigen (EMA) test and multiple time blood transfusions and some of them had a family history of splenectomy.
Using NGS based Redcliffe curated clinical exome sequencing panel and specific bioinformatics analysis pipeline coupled with genotype-phenotype association with the help of a clinician, scientist identifies six novel variants in ANK1 and SPTB genes which are previously implicated in Hereditary Spherocytosis type 1 and 2 in autosomal dominant inheritance mode for six samples.
“All six novel identified variants are reported in accordance with ACMG guidelines and are predicted to produce truncated protein. Out of which, five were identified in the ANK1 gene and one was identified in SPTB gene”, says Dr Deepika Kalo, lead scientist at Redcliffe Lifesciences.
Out of five novel variants in the ANK1 gene, four were classified as “frameshift” and one variant was classified as “nonsense”. The SPTB gene variant was of termination type. All these identified novel truncated variants were classified as “Likely Pathogenic” in these individuals under the study.
“Variants classified as likely pathogenic have sufficient evidence that a healthcare provider can use in clinical decision making when combined with other evidence in question. Many previous research studies reported that the alterations in the ANK1 and SPTB gene lead to Hereditary Spherocytosis”, says Ashish Dubey, co-founder at Redcliffe.
Hereditary Spherocytosis is a disorder characterized by a deficiency in Ankyrin and/or Spectrin genes resulting in the collapse of red blood cell’s lipid bilayer skeleton and thereby loss of membrane as microvesicles which reduces the surface area and make the red blood cells attain a spherical shape. Thus, this study helps in identifying the genetic aetiology of the Hereditary Spherocytosis by associating six different novel variants in two genes. The research is in progress for further functional analysis.
