Tekin Mustafa, Cengiz Filiz Başak, Ayberkin Eda, Kendirli Tanil, Fitoz Suat, Tutar Ercan, Ciftçi Ergin, Conba Atakan
Division of Clinical Molecular Pathology and Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey.
Am J Med Genet A. 2007 Apr 15;143A(8):875-80. doi: 10.1002/ajmg.a.31660.
We present a family in which three siblings were born with neonatal Marfan syndrome (MFS) to unaffected parents. The clinical findings included joint contractures, large ears, loose skin, ectopia lentis, muscular hypoplasia, aortic root dilatation, mitral and tricuspid valve insufficiency, and pulmonary emphysema. All three siblings died due to cardiorespiratory insufficiency by 2-4 months of age. Screening of the FBN1 gene showed the heterozygous c.3257G > A (p.Cys1086Tyr) mutation in the proband. Mosaicism of the mutation was demonstrated in the somatic cells and in the germ line of the father. Although three examples of parental mosaicism for classical MFS were demonstrated previously, this is the first report of familial occurrence of neonatal MFS due to a heterozygous mutation in FBN1. In conclusion, the p.Cys1086Tyr mutation in FBN1 is consistently associated with neonatal MFS. Parental mosaicism should always be kept in mind when counseling families with MFS.
我们报告了一个家庭，该家庭中三个兄弟姐妹出生时患有新生儿马凡综合征（MFS），但其父母未受影响。临床发现包括关节挛缩、大耳朵、皮肤松弛、晶状体异位、肌肉发育不全、主动脉根部扩张、二尖瓣和三尖瓣关闭不全以及肺气肿。所有三个兄弟姐妹均在2至4个月大时因心肺功能不全死亡。对FBN1基因的筛查显示，先证者存在杂合的c.3257G > A（p.Cys1086Tyr）突变。在父亲的体细胞和生殖细胞中均证实了该突变的嵌合现象。尽管此前已证实有三例经典MFS的亲代嵌合现象，但这是首次报道因FBN1杂合突变导致新生儿MFS家族性发病。总之，FBN1基因中的p.Cys1086Tyr突变始终与新生儿MFS相关。在为患有MFS的家庭提供咨询时，应始终考虑亲代嵌合现象。
