Zübeyde DİNÇER, Hatice GÜNEŞ, Nurgül ÇİMEN PARLAK, Saim EKİCİ, Sevcan İPEK, Sadık YURTTUTAN

FRAS1 Gen Mutasyonuna Sahip Fraser Sendromlu Yenidoğan Olgu

Fraser sendromu, otozomal resesif kalıtım modeline sahip seyrek görülen hastalıklardan birisidir. Kriptoftalmus (saklı göz), kulak, burun ve iskelet malformasyonları, sindaktili, laringeal darlık ve ürogenital, akciğer anomalileri ana özelliklerdir. FRAS1, FREM2 ve GRIP1 genlerinde meydana gelen bir takım mutasyonlar sonucunda oluşur. Kesin tanısı gen mutasyonu tespiti ile yapılır.Bu çalışmada Fraser sendromlu FRAS1 mutasyonuna sahip bir olgu sunduk. Olgumuzda çok sayıda anomalinin bir arada olması ve Fraser sendromunun seyrek görülmesi nedeniyle olguyu literatür eşliğinde tartışmayı amaçladık.

A Case of Fraser Syndrome in a Newborn with FRAS1 Gene Mutation

Fraser syndrome is a rare disorder with autosomal recessive inheritance. The main features are cryptophthalmos (hidden eye), ear, nose and skeletal malformations, syndactyly, laryngeal stenosis and malformation of the urogenital system, lungs. It occurs as a result of a number of mutations in the FRAS1, FREM2 and GRIP1 genes. The definitive diagnosis is made by detecting gene mutation. In this study, we presented a case with Fraser syndrome who had FRAS1 mutation. Since Fraser syndrome is a rare disorder and the case had multiple organ anomalies, we aimed to discuss this case in light of the literature.

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1. Fraser Gr. Our genetical load. A reviewof some aspects of genetic variation. Ann Hum Genet 1962;25:387-415.
2.Slavotinek AM, Tift Cj. Fraser syndrome and cryptophthalmos: review of the diagnosis criteria and evidence for phenotypic modules in complex malformation syndromes. J Med Genet 2002;39:623-633.
3.Thomas IT, Frias JL, Felix V, Sanchez de Leon L, Hernandez RA, Jones MC. Isoleted and syndromic cryptophthalmos. Am J Med Genet 1986;25:85-98.
4. Slavotinek A, Li C, Sherr EH, Chudley AE. Mutation analysis of the FRAS1 gene demonstrates new mutations in a propositus with Fraser syndrome. Am J Med Genet A 2006;140A:1909-1914.
5. Smyth I, Scambler P. Genetics of the Fraser syndrome and the blebs mouse mutants. Hum Molec Genet 2005; 14:269-274.
6.Van Haelst MM, Scambler Pj, Fraser syndrome Collaboration Group, Hennekam RC. Fraser Syndrome: A clinical study of 59 cases and evaluation of diagnostic criteria. Am J Med Genet A 2007; 143:3194-203.
7. Dalezious Y, Papasozomenos B, Petrou P, Chalepakis G.Ultrastructural localization of Fras1 in the sublamina densa of embryonic epithelial basement membranes. Arch Dermatol Res 2007; 299:337-343.
8. Long J, Wei Z, Feng W, Yu C, Zhao YX, Zhang M.Supramodular nature of GRIP1 revealed by the structure of its PDZ12 tandem in complex with the carboxyl tail of Fras1. J Mol Biol 2007; doi:10.1016/j.jmb.2007.11.088.
9.Tayman C, Yılmaz A, Tonbul A, Polat E, Kunak B. Fraser sendromu. Yeni Tıp Dergisi 2006;23:163-166.
10.Narang M, Kumar M, Shah D. Fraser-cryphthalmos syndrome with colonic atresia. Indian J Pediatr 2008;75:189-191.
11.Vrontou S, Petrou P, Meyer Bl, et al. Fras1 deficiency results in cryptophthalmos, renal agenesis and blebbed phenotype in mice. Nat Genet 2003;34:209-214.
12.Ramsing M, Rehder H, Holzgreve W, Meinecke P, Lenz W. Fraser syndrome in fetus and newborn. Clin Genet 1990;37:84-96.
13. Janssen HC JP, Schaap C, Vandevijver N, Moerman P, de DieSmulders CEM, Fryns JP. Two sibs with microcephaly, hygroma colli, renal dysplasia, and cutaneous syndactyly: A new lethal MCA syndrome? J Med Genet 1999;35:481-484.