Autosomal recessive Chanarin-Dorfman syndrome (CDS, MIM #275630) is defined as a neutral lipid storage disease with ichthyosis (NLSDI) due to an accumulation of lipid droplets in a variety of different tissues including liver and muscle cells, leucocytes, fibroblasts and nerve cells It is caused by biallelic mutations in the abhydrolase domain containing 5 gene (ABHD5, MIM *604780) which is localized on the short arm of chromosome 3. Here we report an 18 month-old girl in whom we have identified the homozygous ABHD5 mutation c.700C > T, p.(Arg234*). Since none of the parents carried this point mutation, parentage was confirmed by microsatellite marker analysis. Suspected uniparental disomy (UPD) was confirmed by microsatellite genotyping over the entire chromosome 3 and indicated a maternal origin. UPD is an extremely rare event that is not necessarily pathogenic, but may cause disease if the affected chromosome contains genes that are imprinted. Here we report the first case of Chanarin-Dorfman syndrome due to a de novo ABHD5 mutation in the maternal germ cell, combined with a maternal uniparental isodisomy of chromosome 3. This case demonstrates that genetic analysis of the patient and both parents is crucial to provide correct genetic counseling.
Keywords: ABHD5; Chanarin-Dorfman syndrome (CDS); de novo mutation; uniparental disomy (UPD).