Abstract
To describe the utilization of Next Generation Sequencing technologies for genetic
counseling and prenatal diagnosis. Ten families requested prenatal testing in view
of previously affected offspring with genetically heterogeneous/hitherto undiagnosed
disorders. Next generation sequencing was offered as a first tier investigation (1)
in the probands who had not been diagnosed by baseline investigations, and (2) in
cases where preliminary examination/testing suggested a genetically heterogeneous
disorder, while the precise diagnosis was not available. The subsequently identified
molecular basis enabled prenatal testing. The disorders included primary microcephaly,
epidermolysis bullosa, inborn error of metabolism, infantile hypotonia, neuro-regression
and sensorineural hearing loss. Five out of ten couples approached us during an ongoing
pregnancy with two in the second trimester of gestation. Demise of the proband resulted
in incomplete investigations in three cases. In seven cases, the disorder suspected
was genetically heterogeneous and hence next generation testing was carried out while
in the remaining three it was performed to ascertain the underlying gene involved.
Fetal analysis detected recurrences in two cases, and the couples concerned decided
to discontinue the pregnancies. Next generation sequencing proved a useful tool in
select situations to overcome some of the challenges hindering a precise diagnosis
in genetically heterogenous disorders.
Keywords
Multi gene panel - Prenatal diagnosis - Autosomal recessive - Next gen sequencing
