Waardenburg Sendromu'nda Tanımlanan Çok Nadir Bir PAX3 Geni Varyantı: c.232G>A(p.Val78Met)

Öz

Waardenburg Sendromu(WS); İlk olarak PJ Waardenburg tarafından tanımlanmış, deri, saç, göz veya kohleadaki stria vascularis'te melanositlerin fiziksel yokluğundan kaynaklanan hastalıktır. Poliozis (saçta beyaz perçem), hipopigmente maküller, canlı mavi gözler veya heterokromik iris ve sensörinöral işitme kaybı dahil pigmentasyon anormalliklerinin birlikteliği ile karakterizedir. Bu sendromda altı gen mutasyonu suçlanmaktadır. Bunlar; PAX3 (Paired box 3 transkripsiyon faktörün) geni, MITF (Mikroftalmi ile ilişkili transkripsiyon faktörü) geni, EDN3 (Endotelin 3) geni, EDNRB (Endotelin reseptör tip B) geni, SOX10 (Sry bOX10 transkripsiyon faktörü) geni ve SNAI2 (Snail homolog 2) genleridir. Çok nadir bir hastalıktır, prevelansı 1/42000’dir. Kadın ve erkeklerde eşit oranda görülür. Bu yazıda PAX3 geni ekzon 2’de c.232G>A(p.Val78Met) patojenik varyantı tespit edilerek Waardenburg Sendromu teşhisi konan 2 aylık nadir bir olgu sunulmuştur.

Anahtar Kelimeler

• Waardenburg,
• PAX3 Geni
• Sensörinöral İşitme Kaybı

A very Rare PAX3 Gene Variant Identified in Waardenburg Syndrome: C.232G>A(p.Val78Met)

Öz

Waardenburg Syndrome (WS); it was first defined by PJ Waardenburg. This disease is caused by the physical absence of melanocytes in the stria vascularis of the skin, hair, eyes or cochlea. It is characterized by the association of pigmentation abnormalities including poliosis (white forelock on the hair), hypopigmented macules, bright blue eyes or heterochromic iris and sensorineural hearing loss. Six gene mutations are blamed in this syndrome. These; PAX3 (Paired box 3 transcription factor) gene, MITF (Microphthalmia-associated transcription factor) gene, EDN3 (Endothelin 3) gene, EDNRB (Endothelin receptor type B) gene, SOX10 (Sry bOX10 transcription factor) gene and SNAI2 (Snail homolog 2) are genes. It’s a very rare disease, its prevalence is 1/42000. It is seen equally in men and women. In this article, a 2-month-old rare case diagnosed with Waardenburg Syndrome by detecting c.232G> A (p.Val78Met) pathogenic variant in exon 2 of the PAX3 gene is presented.

Anahtar Kelimeler

• Waardenburg
• PAX3 Gene
• Sensorineural Hearing Loss

Kaynakça

1. Referans1. Waardenburg PJ. A new syndrome combining developmental anomalies of the eyelids, eyebrows and nose root with pigmentary defects of the iris and head hair and with congenital deafness. Am J Hum Genet 1951;3:195-253.
2. Referans2. A P Read, V E Newton, Waardenburg syndrome, J Med Genet. 1997 Aug;34(8):656-65.doi: 10.1136/jmg.34.8.656.
3. Referans3. Tosun F, Kertmen M, Yetişer S, Satar B, Özkaptan Y. Waardenburg sendromu: Klinik sınıflama ve üç farklı olgu sunumu. Kulak Burun Boğaz Klinikleri 2000;2:37-40.
4. Referans4. Kılıçarslan H, Eser İ, Şener HM, Akkuş M, Waardenburg sendromu: Olgu sunumu, Genel Tıp Derg 2008;18(4): 173-176.
5. Referans5. Bondurand N, Dastot-Le Moal F, Stanchina L, etal. Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4, Am J Hum Genet. 2007 Dec;81(6):1169-85. doi: 10.1086/522090. Epub 2007 Oct 22.
6. Referans6. Pingault V, Ente D, Dastot-Le Moal F, Goossens M, Marlin S, Bondurand N, Review and update of mutations causing Waardenburg syndrome, Hum Mutat. 2010 Apr;31(4):391-406. doi: 10.1002 /humu.21211.
7. Referans7. Oysu C, Baserer N, Tinaz M. Audiometric manifestations of Waardenburg’s syndrome. Ear Nose Throat J 2000; 79: 704-709.
8. Referans8. Taşkın E, Kılıç M, Aydın M, Ertuğrul S, Denizmen Aygün A, BİR OLGU NEDENİYLE WAARDENBURG SENDROMU, Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi. 2004, Cilt 18, Sayı 4, Sayfa(lar) 251-253.

9. Referans9. Mancini AJ: Waardenburg syndrome type II in a Taiwanese woman with a family history of pseudoxanthoma elasticum. Int J Dermatol 1997; 36: 926-37.
10. Referans10. Konno P., Silm H: Waardenburg syndrome. J. Eur Acad Dermatol Venereol 2001; 15: 330-3.
11. Referans11. Toki F, Suziki N, Inoue K, et al.: Intestinal aganglionosis associated with the Waardenburg syndrome: report of two cases and review of the literature. Ped Surg Int 2003; 19: 725-8.
12. Referans12. Dourmishev AL, Dourmishev LA, Schwartz RA, Janniger CK. Waardenburg syndrome. Int J Dermatol 1999; 38: 656– 663.
13. Referans13. Grundfast KM, Atwood JL, Cuong D. Genetics and molecular biology of deafness. Otolaryngol Clin North Am 1999; 32: 1067- 1088.
14. Referans14. Önder Hİ, Tunç M, Yüksel H, etal. Waardenburg Sendromlu Hastalarda Göz Bulguları, Düzce Tıp Dergisi 2013; 15(3): 60-63.
15. Referans15. Nork TM, Shihab ZM, Young RSL et al.: Pigment distribution in Waardenburg's syndrome: a new hypothesis. Graefe's Arch Clin Exp Ophthalmol 1986;224:487-492.
16. Referans16. Krishtul A, Galadari Y. Waardenburg syndrome: case report. Int J Dermatol 2003;42:651-652.
17. Referans17. Long Cui , Emily Hoi-Man Wong, Guo Cheng, Manoel Firmato de Almeida, etal. Genetic Analyses of a Three Generation Family Segregating Hirschsprung Disease and Iris Heterochromia, PLoS One. 2013 Jun 26;8(6):e66631. doi: 10.1371/journal.pone.0066631. Print 2013.
18. Referans18. Tassabehji M, Newton VE, Liu XZ etal. The Mutational Spectrum in Waardenburg Syndrome. Hum Mol Genet. 1995 Nov;4(11):2131-7.doi:10.1093/hmg/4.11.2131.
19. Referans19. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med [Internet]. 2015 May 5 [cited 2017 Nov 5];17(5):405–23