Question

Read the paper below and answer the accompanying questions.

‘Whole-genome sequencing expands diagnostic utility and improves clinical management in paediatric medicine’ Stavropoulos et al. npj Genomic Medicine 1, Article number: 15012 (2016) doi:10.1038/npjgenmed.2015.12

How successful was the study at reaching conclusive clinically useful diagnoses?

Briefly describe the relationship between the CNV found and one disease phenotype – why does discovery of the variant provide a diagnosis (what gene is affected, how, what has that got to do with the disease?)

Briefly describe the relationship between the variant(s) found and one disease phenotype – why does discovery of the variant provide a diagnosis?

Answer 1

Answer:

How successful was the study at reaching conclusive clinically useful diagnoses?

• In this study, Whole-genome sequencing (WGS) was utilized to identify genetic variants which are useful in clinical diagnosis. In 34% of the cases (out of 100 patients), the WSG technique was able to meet clinical diagnostic criteria which represented a 4-fold increase in diagnostic rate as compared to Chromosome Microarray analysis (CMA) and more than 2-fold increase in CMA plus targeted gene sequencing.

Briefly describe the relationship between the CNV found and one disease phenotype – why does discovery of the variant provide a diagnosis (what gene is affected, how, what has that got to do with the disease?)

• One clinically significant copy-number variant identified by chromosomal microarray and WSG is Chr8:97,134,000–98,308,000 de​l. Category 2. 8q22.1
• This variant is associated with Complex phenotype with two genetic disorders.
  • de novo deletion.
  • Paternally inherited CCM2 pathogenic variant related to Cerebral cavernous malformation (CCM)

Briefly describe the relationship between the variant(s) found and one disease phenotype – why does discovery of the variant provide a diagnosis?

• One clinically significant sequence-level variant identified by WSG technique is c.751A4C(p.Ile251Leu)(het) corresponding to gene MC4R.
• This CNV variant is potentially related to obesity in proband.