Jacobs Amanda M, Toudjarska Ivanka, Racine Andrew, Tsipouras Petros, Kilpatrick Michael W, Shanske Alan
Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.
Arch Pediatr Adolesc Med. 2002 Nov;156(11):1081-5. doi: 10.1001/archpedi.156.11.1081.
Marfan syndrome is an autosomal dominant disorder of connective tissue caused by mutations in the fibrillin 1 gene (FBN1). FBN1 mutations have been associated with a broad spectrum of phenotypes. Neonatal Marfan syndrome has unique clinical manifestations and mutations.
To determine if there is a discernible genotypic-phenotypic correlation associated with the unique mutation in neonatal Marfan syndrome.
A newborn exhibited many typical characteristics of neonatal Marfan syndrome, including arachnodactyly; contractures of both elbows, knees, and ankles; small-joint laxity; dilated cardiomyopathy; valvular dysplasia and insufficiency; congestive heart failure; and pulmonary emphysema. Three atypical features were also discovered: a right diaphragmatic hernia, a myocardial mass, and left main-stem bronchomalacia. She died at 3(1/2) months of age. Total RNA was extracted from skin fibroblasts and amplified by means of reverse transcriptase polymerase chain reaction amplification with FBN1-specific primers. The complementary DNA fragments were sequenced.
A single T-to-C transition at nucleotide 3276 (T3276C) was identified and confirmed at the DNA level by sequencing of genomic DNA. This results in a substitution of threonine for isoleucine.
Neonatal Marfan syndrome is a unique clinical entity with recurring mutation hot spots in exons 24 to 27 and 31 to 32 of the FBN1 gene. Some clinical features in this case report are unusual for neonatal Marfan syndrome. This is the third report of this T3276C mutation in the FBN1 gene with unusual clinical manifestations. We conclude that there is a genotypic-phenotypic correlation associated with this mutation.
马凡综合征是一种常染色体显性结缔组织疾病，由原纤蛋白1基因（FBN1）突变引起。FBN1突变与多种表型相关。新生儿马凡综合征有独特的临床表现和突变。
确定新生儿马凡综合征的独特突变是否存在明显的基因型-表型相关性。
一名新生儿表现出许多新生儿马凡综合征的典型特征，包括蜘蛛指；双肘、双膝和双踝关节挛缩；小关节松弛；扩张型心肌病；瓣膜发育异常和功能不全；充血性心力衰竭；以及肺气肿。还发现了三个非典型特征：右膈疝、心肌肿块和左主支气管软化。她在3个半月大时死亡。从皮肤成纤维细胞中提取总RNA，并使用FBN1特异性引物通过逆转录聚合酶链反应扩增进行扩增。对互补DNA片段进行测序。
在核苷酸3276处发现单个T到C的转换（T3276C），并通过基因组DNA测序在DNA水平得到证实。这导致异亮氨酸被苏氨酸取代。
新生儿马凡综合征是一种独特的临床实体，在FBN1基因的第24至27外显子和第31至32外显子中有反复出现的突变热点。本病例报告中的一些临床特征在新生儿马凡综合征中并不常见。这是FBN1基因中T3276C突变伴不寻常临床表现的第三份报告。我们得出结论，该突变存在基因型-表型相关性。
