Acrofacial dysostosis syndrome of Rodriguez is characterized by severe mandibular underdevelopment, upper limb phocomelia with absent fingers, absent fibulae, cleft palate, microtia, and abnormal pulmonary function. First reported in three siblings it was assumed to be an autosomal recessive condition. However, subsequent publication reported a further five simplex occurrences and a living patient with a heterozygous mutation in the SF3B4 gene. Exome sequencing was performed on four fetuses with this disorder, including one of the originally described affected siblings. We identified two heterozygous frameshift mutations in the SF3B4 gene in three of the four fetuses investigated. The observed mutation was apparently de novo in one fetus for whom parental DNA was available. Thus, Acrofacial dysostosis syndrome of Rodriguez is an autosomal dominant condition and the recurrences identified in the initial report were likely due to gonadal mosaicism.

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American Journal of Medical Genetics. Part A
Erasmus MC: University Medical Center Rotterdam

Irving, M.D. (Melita D.), Dimitrov, B.I. (Boyan I.), Wessels, M., Holder-Espinasse, M., Chitayat, D., & Simpson, M. A. (2016). Rodriguez acrofacial dysostosis is caused by apparently de novo heterozygous mutations in the SF3B4 gene. American Journal of Medical Genetics. Part A, 170(12), 3133–3137. doi:10.1002/ajmg.a.37946