Pontocerebellar hypoplasia type 1B is a severe autosomal recessive neurologic disorder
characterized by a combination of cerebellar and spinal motor neuron degeneration
beginning at birth. Pontocerebellar hypoplasia type 1B is caused by mutations in EXOSC3 gene. High prevalence of the p.Gly31Ala mutation was found recently, especially in
the Roma ethnic minority. We present a young Bulgarian Roma family with two deceased
newborn children manifesting severe neuromuscular disorder including severe muscle
weakness, respiratory distress, and multiple joint contractures. Based on the clinical
signs and family's population characteristics, DNA testing for the previously described
EXOSC3 in Bulgarian Roma mutation c.92G > C; p.Gly31Ala was performed on blood samples of
both parents and they were found to be heterozygous carriers. This finding indirectly
confirmed the diagnosis of pontocerebellar hypoplasia type B in the deceased offspring.
Knowledge of population-specific molecular bases of genetic conditions was the key
to final diagnosis in the presented family. Designing of population-based clinical-genetic
panels may be a powerful diagnostic tool for patients with such origin. Preconception
carrier screening in high-risk population groups is a feasible option to discuss.
Keywords
Pontocerebellar hypoplasia type 1B -
EXOSC3 gene - spinal muscular atrophy - Roma population genetic diseases
