Evidence for preferential X-chromosome inactivation in a family with Fabry disease

Severe clinical signs of Fabry disease were observed in four of eight heterozygous daughters of a male patient. Activities of alpha-galactosidase A in serum, white blood cells, and hair roots of the manifesting carriers were markedly lower than 50% of normal. These findings are not easy to interpret in terms of random X inactivation alone; several alternative models including nonrandom (preferential) X inactivation are discussed.