Sunita Bijarnia-Mahay, Deepti Gupta, V L Ramprasad, Sakthivel Murugan, Renu Saxena, Sudha Kohli, Seiji Yamaguchi, Yosuke Shigematsu and I C Verma, Genetic Clinics 2017, January – March, Vol 10, Issue 1.
Next generation sequencing has changed the approach to genetic diagnosis and testing in recent times. The days have arrived when a molecular genetic diagnosis can be attempted even without the availability of the proband or affected person. However this requires additional strong evidence of diagnosis in the proband, such as biochemical or radiological hallmarks. Needless to say, this attempt should always be made during counseling to make the family aware of the fallacies and limitation involved due to non-availability of the sample of the proband. Since many recessive disorders are either fatal or severely debilitating and burdensome, with no easy treatment, the NGS technology has provided a much needed relief in terms of testing and prevention in family by enabling prenatal diagnosis, at least in a few cases. Encouraging results have been shown upon testing of the proband directly. However, the final word remains to be said on complete reliability of the method for carrier testing, performed without availability of the proband. We present two similar cases, of methyl malonic acidemia, where use of NGS resulted in contrasting outcomes after genetic testing for carrier status, thus highlighting the utility and the futility of the test in certain situations. While a correct identification of mutations in the first couple (in the MMAB gene) resulted in successful prenatal diagnosis and prevention of recurrence, an inability to identify the disease and mutation resulted in birth of an affected baby with MMA in the second family.