Sm. Tanner et al., Skewed X-inactivation in a manifesting carrier of X-linked myotubular myopathy and in her non-manifesting carrier mother, HUM GENET, 104(3), 1999, pp. 249-253
X-linked recessive myotubular myopathy (XLMTM) is a muscle disorder usually
affecting newborn males. In the majority of cases, muscle weakness and hyp
otonia lead to a rapid demise at neonatal age. The responsible MTM1 gene is
located in proximal Xq28. Heterozygous carriers are described as being asy
mptomatic but, in a few cases, mild facial weakness has been reported. We r
eport a family in which a 39-year old female showed severe progressive musc
le weakness. XLMTM was initially diagnosed in the male offspring of one of
the patient's sisters. The patient, one of her sisters, and their mother we
re heterozygous carriers for a common MTM1 gene mutation. We found an extre
mely skewed X-inactivation pattern in the patient and, in the opposite dire
ction, in her non-manifesting carrier mother, thus explaining her normal ph
enotype and indicating a possible inheritance of skewed X-inactivation. Lin
kage analysis excluded a possible involvement of the XIST locus at Xq13.