From genetic data to accurate diagnosis: case study on practical use of NGS data analysis by Intelliseq

Monika Opalek, PhD

July 18, 2023

Precision medicine revolutionizes healthcare by customizing medical decisions and treatments according to an individual's unique genetic makeup and other relevant factors like lifestyle and family disease history. This patient-centered approach empowers healthcare providers to utilize targeted therapies that specifically address the molecular and genetic characteristics of a patient's condition. By doing so, precision medicine reduces the occurrence of side effects while maximizing therapeutic benefits.

Nonetheless, identifying the genetic background associated with a patient's symptoms can pose significant challenges. Therefore, the efficient analysis of genomic data becomes crucial to implement personalized treatment plans on a large scale.

To illustrate the practical application of precision medicine, we present a case study that demonstrates the effectiveness of NGS data analysis by Intelliseq in facilitating diagnosis. The patient experienced non-specific symptoms that were difficult to diagnose using conventional methods. Therefore, to unravel the underlying cause of the patient's condition, whole exome sequencing (WES) was performed. The analysis was conducted using the WES Hereditary Disorders ACMG workflow using only the fastq file and information presented below.

The description of patient phenotype:

A |age|-years-old |person| presented with a history of gradually progressive gait problems. Neurological examination revealed mild spastic paraparesis and decreased vibration sense in toes; otherwise normal. Head MRI showed hiperintense signal in T2-weighted imaging bilaterally in pyramidal tracts and splenium of the corpus callosum. In the nerve conduction study – demyelinating motor and sensory polyneuropathy.

HPO terms assigned:

Gait disturbance HP:0001288

Paraparesis HP:0002385

Impaired vibration sensation in the lower limbs HP:0002166

Abnormal corpus callosum morphology HP:0001273

Sensory neuropathy HP:0000763

Peripheral neuropathy HP:0009830

Demyelinating peripheral neuropathy HP:0007108

A total of 815 genes were included in the gene panel based on the phenotype description and the assigned HPO terms. The analysis was launched with default setting, specifically the genome was aligned to the GRCh38 reference genome with BWA-mem tool


Two pathogenic variants and 18 variants of uncertain significance were identified in the analysis. Notably, both pathogenic variants were identified in the GALC gene, indicating the presence of a compound heterozygote. These variants are associated with a condition known as Krabbe disease, also referred to as globoid cell leukodystrophy.

The diagnosis of Krabbe disease was confirmed by low activity of the beta-galactocerebrosidase in leukocytes. As part of the treatment plan, the patient underwent hematopoietic stem cell transplantation, which yielded positive outcomes. In a follow-up assessment conducted two years later, the patient's neurological symptoms remained stable, and the enzyme activity levels were within the normal range. 

In the case presented, the efficient analysis of genetic data played a crucial role in the diagnosis. The identification of two pathogenic variants in the GALC gene strongly suggested the presence of Krabbe disease, which was subsequently confirmed through specific tests. This timely confirmation facilitated the implementation of an effective treatment plan, resulting in positive outcomes. The successful use of genetic data in this case was a fundamental step in the accurate diagnosis of the disease. 

Disclaimer: All personal data in this article have been anonymized to ensure privacy and confidentiality. The patient involved in this case study willingly consented to the use of their data for the purpose of this article.

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