A recent study in Brain1 identified two homozygous missense variants in RNF220 [p.(R363Q) and p.(R365Q)] in five European pedigrees with ataxia, deafness, hypomyelinating leukodystrophy, liver dysfunction and dilated cardiomyopathy. The R365Q mutation was found in four families of Roma ethnic origin and proposed to be a founder mutation. However, here, we report a sixth family, of Chinese ethic descent, with the same p.(R363Q) variant. We also discuss the origin of this recurrence. Our patient, a 7-year-old boy, is the eighth pregnancy of a consanguineous Chinese couple. The couple’s mothers are sisters. The first three children were born prematurely in the seventh or eighth month of pregnancy, and the fourth child was born at term, all of whom were stillborn girls. The fifth child was a boy who presented with hand tremor at 1 year of age, and with hearing loss at 7 years of age. He died at the age of 9 years with fever and wheezing. The condition of the heart is unclear. Pale hair colour was also recorded. The sixth and seventh foetuses were aborted for personal reasons. At the age of 47 years, the mother gave birth to their eighth child, the index patient in this study (Fig. 1). The boy was born uneventfully at full term by caesarean section due to his mother’s advanced age. His birth weight was 2.8 kg. He could walk alone stably and speak at age 1. Other developmental milestones were also in the normal range, except for intention tremor in both hands emerging at the age of 1 year. Hearing loss was noted at 5 years old, and worsened quickly to complete hearing loss at age 7 years. Dysarthria appeared along with hearing loss. Cognitive ability is spared. Neither abnormal gait nor seizures were noted. Examined at 5 years of age, pale hair colour for hair and eyebrows, hyperreflexia, positive Babbitt sign and finger-nose test were recorded. Head circumference, eye movement, muscle strength and tension were all normal. Brain MRI performed at age 5 years of age demonstrated diffuse hypomyelination, thin corpus callosum, slightly atrophied cerebellum and decreased T2-weighted signals in bilateral pallidus globus and lentiform nucleus (Fig. 2). His heart function was normal and cardiac ultrasonography was not performed. Kidney function, lactic acid electrolyte and inborn metabolic error screening were all normal. For liver function, AST 15 IU/l is normal and ALT 48 IU/l is borderline.
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