Journal of Interdisciplinary Genomics

유전의학융합회 (Interdisciplinary Society of Genetic & Genomic Medicine)
권호 표지
DOI QR코드

DOI QR Code

Searching for the Missing Kallmann Syndrome Gene at 9q31.3

  • Hyung-Goo Kim (Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, the State University of New Jersey) ;
  • Sang Hoon Lee (Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, the State University of New Jersey) ;
  • Lawrence C. Layman (Section of Reproductive Endocrinology, Infertility & Genetics, Department of Obstetrics & Gynecology, Augusta University) ;
  • Mi-Hyeon, Jang (Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, the State University of New Jersey)
  • 투고 : 2024.08.30
  • 심사 : 2024.10.07
  • 발행 : 2024.10.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

The disease gene for delayed puberty is hypothesized to reside within a 3.7 Mb genomic region on chromosome 9, spanning 9q31.2 to 9q31.3, which contains 20 genes. This region aligns with 9q31.3, where the Kallmann syndrome gene is suspected to be located in a patient with a de novo balanced translocation, t(7;9)(p14.1;q31.3). After analyzing the expression patterns and reported genetic variants of the 20 candidate genes, we propose ACTL7A and ACTL7B as strong candidate genes for Kallmann syndrome. Mutation screening of these genes in Kallmann syndrome patients will be essential to confirm their pathological roles in delayed puberty.

키워드

참고문헌

  1. Ramineni AK, Burgess T, Cruickshanks P, Coman D. A novel familial 9q31.2q32 microdeletion: muscle cramping, somnolence, fatigue, sensorineural hearing loss, pubertal delay, and short stature. Clin Case Rep 2019;7(2):304-10. doi: 10.1002/ccr3.1970.
  2. Panza E, Gimelli G, Passalacqua M, Cohen A, Gimelli S, Giglio S, et al. The breakpoint identified in a balanced de novo translocation t(7;9)(p14.1;q31.3) disrupts the A-kinase (PRKA) anchor protein 2 gene (AKAP2) on chromosome 9 in a patient with Kallmann syndrome and bone anomalies. Int J Mol Med 2007; 19(3):429-35. doi: 10.3892/ijmm.19.3.429.
  3. Warburton D. De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints. Am J Hum Genet 1991;49(5):995-1013.
  4. Kleinjan DA, van Heyningen V. Long-range control of gene expression: emerging mechanisms and disruption in disease. Am J Hum Genet 2005;76(1):8-32. doi: 10.1086/426833.
  5. Kim HG, Kim HT, Leach NT, Lan F, Ullmann R, Silahtaroglu A, et al. Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies. Am J Hum Genet 2012;91(1):56-72. doi: 10.1016/j.ajhg.2012.05.005.
  6. Bhagavath B, Layman LC. The genetics of hypogonadotropic hypogonadism. Semin Reprod Med 2007;25(4):272-86. doi: 10.1055/s-2007-980221.
  7. Xu M, Zhou H, Yong J, Cong P, Li C, Yu Y, et al. A Chinese patient with KBG syndrome and a 9q31.2-33.1 microdeletion. Eur J Med Genet 2013;56(5):245-50. doi: 10.1016/j.ejmg.2013.01.007.
  8. Chadwick BP, Mull J, Helbling LA, Gill S, Leyne M, Robbins CM, et al. Cloning, mapping, and expression of two novel actin genes, actin-like-7A (ACTL7A) and actin-like-7B (ACTL7B), from the familial dysautonomia candidate region on 9q31. Genomics 1999;58(3):302-9. doi: 10.1006/geno.1999.5848.
  9. Frankel S, Mooseker MS. The actin-related proteins. Curr Opin Cell Biol 1996;8(1):30-7. doi: 10.1016/s0955-0674(96)80045-7.
  10. Xin A, Qu R, Chen G, Zhang L, Chen J, Tao C, et al. Disruption in ACTL7A causes acrosomal ultrastructural defects in human and mouse sperm as a novel male factor inducing early embryonic arrest. Sci Adv 2020;6(35):eaaz4796. doi: 10.1126/sciadv. aaz4796.
  11. Wang J, Zhang J, Sun X, Lin Y, Cai L, Cui Y, et al. Novel bi-allelic variants in ACTL7A are associated with male infertility and total fertilization failure. Hum Reprod 2021;36(12):3161-9. doi: 10.1093/humrep/deab228.
  12. Wang M, Zhou J, Long R, Jin H, Gao L, Zhu L, et al. Novel ACTL7A variants in males lead to fertilization failure and male infertility. Andrology 2023. doi: 10.1111/andr.13553.
  13. Zhao S, Cui Y, Guo S, Liu B, Bian Y, Zhao S, et al. Novel variants in ACTL7A and PLCZ1 are associated with male infertility and total fertilization failure. Clin Genet 2023;103(5):603-8. doi: 10.1111/cge.14293.
  14. Zhou X, Xi Q, Jia W, Li Z, Liu Z, Luo G, et al. A novel homozygous mutation in ACTL7A leads to male infertility. Mol Genet Genomics 2023;298(2):353-60. doi: 10.1007/s00438-022-01985-0.
  15. Zhou J, Zhang B, Zeb A, Ma A, Chen J, Zhao D, et al. A recessive ACTL7A founder variant leads to male infertility due to acrosome detachment in Pakistani Pashtuns. Clin Genet 2023;104(5):564-70. doi: 10.1111/cge.14383.