Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
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A neonate with Say-Barber-Biesecker-Young-Simpson syndrome with a novel pathogenic mutation in KAT6B gene: A case report

  • Shin, Ji Hye (Department of Pediatrics, Chungnam National University Hospital) ;
  • Lim, Han Hyuk (Department of Pediatrics, Chungnam National University Hospital) ;
  • Gang, Mi Hyeon (Department of Pediatrics, Chungnam National University Hospital) ;
  • Kim, Seon Young (Department of Laboratory Medicine, Chungnam National University College of Medicine) ;
  • Yang, Shin-seung (Department of Physical Medicine and Rehabilitation, Chungnam National University Hospital) ;
  • Chang, Mea-young (Department of Pediatrics, Chungnam National University Hospital)
  • Received : 2021.10.16
  • Accepted : 2021.11.15
  • Published : 2021.12.31
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Abstract

The Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) (Online Mendelian Inheritance in Man #603736) is a rare autosomal dominant disorder and clinically features blepharophimosis with ptosis, a mask-like facial appearance, cryptorchidism, congenital heart defect, long thumbs/great toes, and thyroid dysfunction. The etiology of SBBYSS has been shown to be due to heterozygous KAT6B gene mutation. Here we report a case of a neonate with SBBYSS identified a novel mutation in KAT6B gene. The patient showed typical dysmorphic facies, cryptorchidism with micropenis, overriding fingers, and long thumbs and toes at birth. He had also hypothyroidism, large atrial septal defect, and sensorineural hearing loss. The next generation sequencing identified a heterozygous novel variant, c.5206C>T (p.Gln1736Ter) in KAT6B gene. At the 9 months of age, he underwent patch closure for atrial septal defect. Until the 12-month follow-up, he was under-developed.

Keywords

Acknowledgement

This work was supported by research fund of Chungnam National University.

References

  1. Clayton-Smith J, O'Sullivan J, Daly S, Bhaskar S, Day R, Anderson B, et al. Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome. Am J Hum Genet 2011;89:675-81. https://doi.org/10.1016/j.ajhg.2011.10.008
  2. Kraft M, Cirstea IC, Voss AK, Thomas T, Goehring I, Sheikh BN, et al. Disruption of the histone acetyltransferase MYST4 leads to a Noonan syndrome-like phenotype and hyperactivated MAPK signaling in humans and mice. J Clin Invest 2011;121:3479-91. https://doi.org/10.1172/JCI43428
  3. Simpson MA, Deshpande C, Dafou D, Vissers LE, Woollard WJ, Holder SE, et al. De novo mutations of the gene encoding the histone acetyltransferase KAT6B cause Genitopatellar syndrome. Am J Hum Genet 2012;90:290-4. https://doi.org/10.1016/j.ajhg.2011.11.024
  4. Zhang LX, Lemire G, Gonzaga-Jauregui C, Molidperee S, Galaz-Montoya C, Liu DS, et al. Further delineation of the clinical spectrum of KAT6B disorders and allelic series of pathogenic variants. Genet Med 2020;22:1338-47. https://doi.org/10.1038/s41436-020-0811-8
  5. Lemire G, Campeau PM, Lee BH. KAT6B Disorders. 2012 Dec 13 [Updated 2020 Jan 2]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. [https://www.ncbi.nlm.nih.gov/books/NBK114806/]
  6. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al.; ACMG Laboratory Quality Assurance Committee. 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 2015;17:405-24. https://doi.org/10.1038/gim.2015.30
  7. Ohdo S, Madokoro H, Sonoda T, Hayakawa K. Mental retardation associated with congenital heart disease, blepharophimosis, blepharoptosis, and hypoplastic teeth. J Med Genet 1986;23:242-4. https://doi.org/10.1136/jmg.23.3.242
  8. Say B, Barber N. Mental retardation with blepharophimosis. J Med Genet 1987;24:511.
  9. Biesecker LG. The Ohdo blepharophimosis syndrome: a third case. J Med Genet 1991;28:131-4. https://doi.org/10.1136/jmg.28.2.131
  10. Young ID, Simpson K. Unknown syndrome: abnormal facies, congenital heart defects, hypothyroidism, and severe retardation. J Med Genet 1987;24:715-6. https://doi.org/10.1136/jmg.24.11.715
  11. Vlckova M, Simandlova M, Zimmermann P, Stranecky V, Hartmannova H, Hodanova K, et al. A patient showing features of both SBBYSS and GPS supports the concept of a KAT6B-related disease spectrum, with mutations in mid-exon 18 possibly leading to combined phenotypes. Eur J Med Genet 2015;58:550-5. https://doi.org/10.1016/j.ejmg.2015.09.004
  12. Cormier-Daire V, Chauvet ML, Lyonnet S, Briard ML, Munnich A, Le Merrer M. Genitopatellar syndrome: a new condition comprising absent patellae, scrotal hypoplasia, renal anomalies, facial dysmorphism, and mental retardation. J Med Genet 2000;37:520-4. https://doi.org/10.1136/jmg.37.7.520
  13. Mendez R, Delea M, Dain L, Rittler M. A novel pathogenic frameshift variant of KAT6B identified by clinical exome sequencing in a newborn with the Say-Barber-Biesecker-Young-Simpson syndrome. Clin Dysmorphol 2020;29:42-5. https://doi.org/10.1097/mcd.0000000000000270
  14. Niida Y, Mitani Y, Kuroda M, Yokoi A, Nakagawa H, Kato A. A SayBarber-Biesecker-Young-Simpson variant of Ohdo syndrome with a KAT6B 10-base pair palindromic duplication: a recurrent mutation causing a severe phenotype mixed with genitopatellar syndrome. Congenit Anom (Kyoto) 2017;57:86-8. https://doi.org/10.1111/cga.12196
  15. Radvanszky J, Hyblova M, Durovcikova D, Hikkelova M, Fiedler E, Kadasi L, et al. Complex phenotypes blur conventional borders between Say-Barber-Biesecker-Young-Simpson syndrome and genitopatellar syndrome. Clin Genet 2017;91:339-43. https://doi.org/10.1111/cge.12840
  16. Kim YR, Park JB, Lee YJ, Hong MJ, Kim HT, Kim HJ. Identifying the KAT6B mutation via diagnostic exome sequencing to diagnose Say-Barber-Biesecker-Young-Simpson syndrome in three generations of a family. Ann Rehabil Med 2017;41:505-10. https://doi.org/10.5535/arm.2017.41.3.505
  17. Kim BR, Han JH, Shin JE, Park MS, Park KI, Namgung R, et al. Genitopatellar syndrome secondary to de novo KAT6B mutation: the first genetically confirmed case in South Korea. Yonsei Med J 2019;60:395-8. https://doi.org/10.3349/ymj.2019.60.4.395