Division of Medical Genetics, Department of Pediatrics, Loma Linda University Medical Center, Loma Linda, CA 92354, USA.
Genet Med. 2009 Nov;11(11):769-75. doi: 10.1097/GIM.0b013e3181bd3d90.
FG syndrome is a rare X-linked multiple congenital anomaly-cognitive impairment disorder caused by the p.R961W mutation in the MED12 gene. We identified all known patients with this mutation to delineate their clinical phenotype and devise a clinical algorithm to facilitate molecular diagnosis. We ascertained 23 males with the p.R961W mutation in MED12 from 9 previously reported FG syndrome families and 1 new family. Six patients are reviewed in detail. These 23 patients were compared with 48 MED12 mutation-negative patients, who had the clinical diagnosis of FG syndrome. Traits that best discriminated between these two groups were chosen to develop an algorithm with high sensitivity and specificity for the p.R961W MED12 mutation. FG syndrome has a recognizable dysmorphic phenotype with a high incidence of congenital anomalies. A family history of X-linked mental retardation, deceased male infants, and/or multiple fetal losses was documented in all families. The algorithm identifies the p.R961W MED12 mutation-positive group with 100% sensitivity and 90% specificity. The clinical phenotype of FG syndrome defines a recognizable pattern of X-linked multiple congenital anomalies and cognitive impairment. This algorithm can assist the clinician in selecting the patients for testing who are most likely to have the recurrent p.R961W MED12 mutation.
FG 综合征是一种罕见的 X 连锁多发性先天异常-认知障碍疾病，由 MED12 基因中的 p.R961W 突变引起。我们鉴定了所有已知的携带该突变的患者，以描绘其临床表型并设计临床算法以促进分子诊断。我们从 9 个先前报道的 FG 综合征家族和 1 个新家族中确定了 23 名携带 MED12 中的 p.R961W 突变的男性患者。对其中 6 名患者进行了详细回顾。将这 23 名患者与 48 名 MED12 突变阴性的 FG 综合征患者进行比较。选择能最好地区分这两组的特征来开发一种具有高灵敏度和特异性的算法，以检测 p.R961W MED12 突变。FG 综合征具有可识别的发育异常表型，先天异常发生率较高。所有家族均有 X 连锁智力障碍的家族史、死亡的男婴和/或多次胎儿丢失的记录。该算法以 100%的灵敏度和 90%的特异性识别出 p.R961W MED12 突变阳性组。FG 综合征的临床表型定义了一种可识别的 X 连锁多发性先天异常和认知障碍模式。该算法可以帮助临床医生选择最有可能携带复发性 p.R961W MED12 突变的患者进行检测。
