A novel mutation of HOXA13 in a family with hand-foot-genital syndrome and the role of polyalanine expansions in the spectrum of Müllerian fusion anomalies

ObjectiveTo report a novel mutation found in a family with hand-foot-genital syndrome (HFGS). To characterize the genetic basis of true HFGS versus presence of non-HFGS-related uterovaginal septa.DesignCase-control study.SettingAcademic medical center.Patient(s)The HFGS patients and family members; women with uterine or uterovaginal septa without other sequelae of HFGS.Intervention(s)Sequence analysis of HOXA13 in members of a family with HFGS (3 affected, 1 unaffected); sequence analysis of HOXA13 in biopsy samples obtained from 17 non-HFGS patients with idiopathic uterine or uterovaginal septa and in 11 normal controls.Main Outcome Measure(s)Presence or absence of mutations of HOXA13.Result(s)Affected members of a family with HFGS showed a novel expansion of the third polyalanine tract of HOXA13, inserting 10 alanines in-frame. None of the patients with idiopathic uterovaginal septa displayed mutations of HOXA13.Conclusion(s)The cause of uterovaginal septa without hand and foot symptoms differs from true HFGS. When patients present with septa, it is not necessary to subject them to roentgenograms of the distal limbs or to sequence analysis of HOXA13 unless they show clear signs of the other sequelae characteristic of true HFGS.