Castori Marco, Bottillo Irene, D'Angelantonio Daniela, Morlino Silvia, De Bernardo Carmelilia, Scassellati Sforzolini Giovanna, Silvestri Evelina, Grammatico Paola
Division of Medical Genetics, Department of Molecular Medicine, Sapienza University, Rome, Italy.
Division of Obstetrics and Gynecology, Division of Pathology, San Camillo-Forlanini Hospital, Rome, Italy.
Mol Syndromol. 2014 Aug;5(5):241-4. doi: 10.1159/000365769. Epub 2014 Aug 5.
Nager syndrome, or acrofacial dysostosis type 1 (AFD1), is a rare multiple malformation syndrome characterized by hypoplasia of first and second branchial arches derivatives and appendicular anomalies with variable involvement of the radial/axial ray. In 2012, AFD1 has been associated with dominant mutations in SF3B4. We report a 22-week-old fetus with AFD1 associated with diaphragmatic hernia due to a previously unreported SF3B4 mutation (c.35-2A>G). Defective diaphragmatic development is a rare manifestation in AFD1 as it is described in only 2 previous cases, with molecular confirmation in 1 of them. Our molecular finding adds a novel pathogenic splicing variant to the SF3B4 mutational spectrum and contributes to defining its prenatal/fetal phenotype.
纳杰尔综合征，即1型颌面肢体发育不全（AFD1），是一种罕见的多发畸形综合征，其特征为第一和第二鳃弓衍生物发育不全以及四肢畸形，桡骨/轴射线受累情况不一。2012年，AFD1被发现与SF3B4的显性突变有关。我们报告了一名22周大的患有AFD1的胎儿，该胎儿因一种先前未报道的SF3B4突变（c.35-2A>G）而患有膈疝。膈发育缺陷在AFD1中是一种罕见表现，此前仅在2例病例中有所描述，其中1例有分子学证实。我们的分子学发现为SF3B4突变谱增添了一种新的致病性剪接变异，并有助于明确其产前/胎儿表型。
