Recurrence of CCHS associated PHOX2B poly-alanine expansion mutation due to maternal mosaicism

Abstract

Heterozygous in frame trinucleotide duplications within the PHOX2B gene, leading to poly-alanine expansions, cause Congenital Central Hypoventilation Syndrome. Here we report about a CCHS patient, carrying a +13Ala PHOX2B expansion, whose asymptomatic mother resulted with a low level of mosaicism for the same mutation in peripheral blood cells. Her second pregnancy ended with the spontaneous miscarriage of a fetus who had inherited the PHOX2B mutation, thus confirming germline mosaicism in the mother and the need of proper genetic counseling to CCHS families.

Keywords: PHOX2B polyalanine expansion; capillary electrophoresis of fluorescent amplimers; congenital central hypoventilation syndrome (CCHS); disease recurrence; genetic counseling; somatic mosaicism.