DHX37基因在性发育异常中作用的研究进展

doi:10.3969/j.issn.1674-8115.2024.11.015

上海交通大学学报（医学版） ›› 2024, Vol. 44 ›› Issue (11): 1466-1471.doi: 10.3969/j.issn.1674-8115.2024.11.015

• 综述 • 上一篇

DHX37基因在性发育异常中作用的研究进展

刘蓓(), 贺静()

昆明理工大学附属医院，云南省第一人民医院医学遗传科，昆明 650032

收稿日期:2024-02-06 接受日期:2024-06-24 出版日期:2024-11-28 发布日期:2024-11-28
通讯作者: 贺静 E-mail:1228960209@qq.com;hejing1211@163.com
作者简介:刘　蓓（1998—），女，硕士生；电子信箱：1228960209@qq.com。
基金资助:
云南省技术创新人才培养项目(2019HB071)

Research progress in the role of DHX37 gene in disorders of sex development

LIU Bei(), HE Jing()

The Affiliated Hospital of Kunming University of Science and Technology, Department of Medical Genetics, The First People's Hospital of Yunnan Province, Kunming 650032, China

Received:2024-02-06 Accepted:2024-06-24 Online:2024-11-28 Published:2024-11-28
Contact: HE Jing E-mail:1228960209@qq.com;hejing1211@163.com
Supported by:
Technical Innovation Personnel Training Project in Yunnan Province(2019HB071)

摘要/Abstract

摘要：

性发育异常（disorders of sex development，DSD）是一类临床表型异质性很强的疾病，患病率为1/5 000~1/4 500。根据国际分类标准，按照染色体核型分类，DSD分为性染色体DSD、46，XY DSD和46，XX DSD，仅35%~45%的46，XY DSD患者和10%的46，XX DSD患者的病因能够明确。DSD的表型和致病机制仍然是目前的研究热点。DEAH-box解旋酶37（DEAH-box helicase 37，DHX37）基因是2019年新发现的性发育异常候选致病基因。近年来，研究者们证实了DHX37基因的变异与46，XY DSD疾病有着密切的联系。DHX37基因作为基因组中最保守的基因之一，其诊断较为困难，并且DHX37基因如何导致46，XY DSD疾病的分子机制尚不清楚。近年来，许多研究者通过全外显子组基因测序技术筛选出DHX37基因的变异位点并对其致病机制进行深入研究，扩展了有关性发育异常的遗传图谱。该文综述了DHX37基因的结构与功能，DHX37基因变异引起的临床表型和DSD的致病机制，以及DHX37基因变异在核糖体病背景下的致病机制。

关键词: 性发育异常, 46，XY DSD, DHX37基因, 人类疾病

Abstract:

Disorders of sex development (DSD) are a group of conditions with strong clinical phenotype heterogeneity, and the incidence of DSD in the population is 1/5 000 to 1/4 500. According to the international classification standards, DSD is divided into sex chromosome DSD, 46,XY DSD and 46,XX DSD according to chromosomal karyotype. Only 35%?45% of patients with 46,XY DSD and 10% of those with 46,XX DSD have definite etiologies. So far, the phenotype and pathogenic mechanism of DSD are still the focus of research. DEAH-box helicase 37 (DHX37) is a novel candidate pathogenic gene for DSD, first identified in 2019. In recent years, researchers have confirmed that DHX37 gene variants are closely related to 46,XY DSD. DHX37 gene is one of the most conserved genes across genomes, making its genetic diagnosis difficult, and the molecular mechanism in causing 46,XY DSD is still unclear. In recent years, many researchers have screened the variation sites of the DHX37 gene by whole exome sequencing (WES) technology and explored its pathogenic mechanisms, which has expanded the genetic map of DSD. This article reviews the relationship between the structure and function of the DHX37 gene, the pathogenic mechanisms of clinical phenotypes and DSD caused by DHX37 gene variants. It also discusses the pathogenic mechanisms of human diseases in the context of ribosomal-related diseases caused by DHX37 gene variants.

Key words: disorders of sex development (DSD), 46,XY DSD, DHX37 gene, human disease

中图分类号:

R588.1

刘蓓, 贺静. DHX37基因在性发育异常中作用的研究进展[J]. 上海交通大学学报（医学版）, 2024, 44(11): 1466-1471.

LIU Bei, HE Jing. Research progress in the role of DHX37 gene in disorders of sex development[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(11): 1466-1471.

参考文献 50

1	GARCÍA-ACERO M, MORENO O, SUÁREZ F, et al. Disorders of sexual development: current status and progress in the diagnostic approach[J]. Curr Urol, 2020, 13(4): 169-178.
2	GOMES N L, CHETTY T, JORGENSEN A, et al. Disorders of sex development-novel regulators, impacts on fertility, and options for fertility preservation[J]. Int J Mol Sci, 2020, 21(7): 2282.
3	IBBA A, DEL PISTOIA M, BALSAMO A, et al. Differences of sex development in the newborn: from clinical scenario to molecular diagnosis[J]. Minerva Pediatr, 2021, 73(6): 606-620.
4	KIM J H, KANG E, HEO S H, et al. Diagnostic yield of targeted gene panel sequencing to identify the genetic etiology of disorders of sex development[J]. Mol Cell Endocrinol, 2017, 444: 19-25.
5	YU B Q, LIU Z X, GAO Y J, et al. Prevalence of gene mutations in a Chinese 46, XY disorders of sex development cohort detected by targeted next-generation sequencing[J]. Asian J Androl, 2021, 23(1): 69-73.
6	BERTELLONI S, TYUTYUSHEVA N, VALIANI M, et al. Disorders/differences of sex development presenting in the newborn with 46, XY karyotype[J]. Front Pediatr, 2021, 9: 627281.
7	WISNIEWSKI A B, BATISTA R L, COSTA E M F, et al. Management of 46, XY differences/disorders of sex development (DSD) throughout life[J]. Endocr Rev, 2019, 40(6): 1547-1572.
8	YU B Q, GAO Y J, MAO J F, et al. Mutation of c.244G>T in NR5A1 gene causing 46, XY DSD by affecting RNA splicing[J]. Orphanet J Rare Dis, 2021, 16(1): 370.
9	AHMED S F, BASHAMBOO A, LUCAS-HERALD A, et al. Understanding the genetic aetiology in patients with XY DSD[J]. Br Med Bull, 2013, 106: 67-89.
10	BASHAMBOO A, MCELREAVEY K. Mechanism of sex determination in humans: insights from disorders of sex development[J]. Sex Dev, 2016, 10(5/6): 313-325.
11	ROCHA V B, GUERRA-JÚNIOR G, MARQUES-DE-FARIA A P, et al. Complete gonadal dysgenesis in clinical practice: the 46, XY karyotype accounts for more than one third of cases[J]. Fertil Steril, 2011, 96(6): 1431-1434.
12	UEHARA S, HASHIYADA M, SATO K, et al. Complete XY gonadal dysgenesis and aspects of the SRY genotype and gonadal tumor formation[J]. J Hum Genet, 2002, 47(6): 279-284.
13	DANNHEISIG D P, BÄCHLE J, TASIC J, et al. The Wnt/β-catenin pathway is activated as a novel nucleolar stress response[J]. J Mol Biol, 2021, 433(2): 166719.
14	廖立红, 钟敏, 付学东, 等. DHX37基因突变致46, XY睾丸退化综合征临床分析及文献复习[J]. 中国优生与遗传杂志. 2023, 31(6): 1237-1240.
	LIAO L H, ZHONG M, FU X D, et al. 46, XY testicular regression syndrome due to heterozygous variant of DHX37 gene and literature review[J]. Chinese Journal of Birth Health and Heredity, 2023, 31(6): 1237-1240.
15	DA SILVA T E, GOMES N L, LERÁRIO A M, et al. Genetic evidence of the association of DEAH-box helicase 37 defects with 46, XY gonadal dysgenesis spectrum[J]. J Clin Endocrinol Metab, 2019, 104(12): 5923-5934.
16	JANKOWSKY E, FAIRMAN M E. RNA helicases: one fold for many functions[J]. Curr Opin Struct Biol, 2007, 17(3): 316-324.
17	DONG Y L, YI Y T, YAO H, et al. Targeted next-generation sequencing identification of mutations in patients with disorders of sex development[J]. BMC Med Genet, 2016, 17: 23.
18	CHOUDHURY P, HACKERT P, MEMET I, et al. The human RNA helicase DHX37 is required for release of the U3 snoRNP from pre-ribosomal particles[J]. RNA Biol, 2019, 16(1): 54-68.
19	HUANG K, PANG T D, TONG C J, et al. Integrative expression and prognosis analysis of DHX37 in human cancers by data mining[J]. Biomed Res Int, 2021, 2021: 6576210.
20	DE LA CRUZ J, KRESSLER D, LINDER P. Unwinding RNA in Saccharomyces cerevisiae: dead-box proteins and related families[J]. Trends Biochem Sci, 1999, 24(5): 192-198.
21	BLEICHERT F, BASERGA S J. The long unwinding road of RNA helicases[J]. Mol Cell, 2007, 27(3): 339-352.
22	NIKOLAY R, SCHMIDT S, SCHLÖMER R, et al. Ribosome assembly as antimicrobial target[J]. Antibiotics, 2016, 5(2): 18.
23	ANGER A M, ARMACHE J P, BERNINGHAUSEN O, et al. Structures of the human and Drosophila 80S ribosome[J]. Nature, 2013, 497(7447): 80-85.
24	HAMMERLING M J, FRITZ B R, YOESEP D J, et al. In vitro ribosome synthesis and evolution through ribosome display[J]. Nat Commun, 2020, 11(1): 1108.
25	PECORARO A, PAGANO M, RUSSO G, et al. Ribosome biogenesis and cancer: overview on ribosomal proteins[J]. Int J Mol Sci, 2021, 22(11): 5496.
26	VON WALDEN F. Ribosome biogenesis in skeletal muscle: coordination of transcription and translation[J]. J Appl Physiol, 2019, 127(2): 591-598.
27	MICOL-PONCE R, SARMIENTO-MAÑÚS R, RUIZ-BAYÓN A, et al. Arabidopsis ribosomal RNA processing 7 is required for 18S rRNA maturation[J]. Plant Cell, 2018, 30(11): 2855-2872.
28	VOS T J, KOTHE U. snR30/U17 small nucleolar ribonucleoprotein: a critical player during ribosome biogenesis[J]. Cells, 2020, 9(10): 2195.
29	MCELREAVEY K, PAILHOUX E, BASHAMBOO A. DHX37 and 46, XY DSD: a new ribosomopathy?[J]. Sex Dev, 2022, 16(2/3): 194-206.
30	LAU B, CHENG J D, FLEMMING D, et al. Structure of the maturing 90S pre-ribosome in association with the RNA exosome[J]. Mol Cell, 2021, 81(2): 293-303.e4.
31	MULLINEUX S T, LAFONTAINE D L J. Mapping the cleavage sites on mammalian pre-rRNAs: where do we stand?[J]. Biochimie, 2012, 94(7): 1521-1532.
32	OBORSKÁ-OPLOVÁ M, FISCHER U, ALTVATER M, et al. Eukaryotic ribosome assembly and nucleocytoplasmic transport[J]. Methods Mol Biol, 2022, 2533: 99-126.
33	HIRATA H, OGINO K, YAMADA K, et al. Defective escape behavior in DEAH-box RNA helicase mutants improved by restoring glycine receptor expression[J]. J Neurosci, 2013, 33(37): 14638-14644.
34	KARACA E, HAREL T, PEHLIVAN D, et al. Genes that affect brain structure and function identified by rare variant analyses of Mendelian neurologic disease[J]. Neuron, 2015, 88(3): 499-513.
35	PAINE I, POSEY J E, GROCHOWSKI C M, et al. Paralog studies augment gene discovery: DDX and DHX genes[J]. Am J Hum Genet, 2019, 105(2): 302-316.
36	MCELREAVEY K, JORGENSEN A, EOZENOU C, et al. Pathogenic variants in the DEAH-box RNA helicase DHX37 are a frequent cause of 46, XY gonadal dysgenesis and 46, XY testicular regression syndrome[J]. Yearb Paediatr Endocrinol, 2020: 293-308.
37	KUTNEY K, KONCZAL L, KAMINSKI B, et al. Challenges in the diagnosis and management of disorders of sex development[J]. BIRTH DEFECTS RES C, 2016, 108(4): 293-308.
38	BUONOCORE F, CLIFFORD-MOBLEY O, KING T F J, et al. Next-generation sequencing reveals novel genetic variants (SRY, DMRT1, NR5A1, DHH, DHX37) in adults with 46, XY DSD[J]. J Endocr Soc, 2019, 3(12): 2341-2360.
39	ZIDOUNE H, MARTINERIE L, TAN D S, et al. Expanding DSD phenotypes associated with variants in the DEAH-box RNA helicase DHX37[J]. Sex Dev, 2021, 15(4): 244-252.
40	AUDI L, AHMED S F, KRONE N, et al. Genetics in endocrinology: approaches to molecular genetic diagnosis in the management of differences/disorders of sex development (DSD): position paper of EU COST Action BM 1303 'DSDnet'[J]. Eur J Endocrinol, 2018, 179(4): R197-R206.
41	DUMESIC D A, LESNICK T G, ABBOTT D H. Increased adiposity enhances intrafollicular estradiol levels in normoandrogenic ovulatory women receiving gonadotropin-releasing hormone analog/recombinant human follicle-stimulating hormone therapy for in vitro fertilization[J]. J Clin Endocrinol Metab, 2007, 92(4): 1438-1441.
42	SREENIVASAN R, JIANG J H, WANG X G, et al. Gonad differentiation in zebrafish is regulated by the canonical Wnt signaling pathway[J]. Biol Reprod, 2014, 90(2): 45.
43	EDMAN C D, WINTERS A J, PORTER J C, et al. Embryonic testicular regression. A clinical spectrum of XY agonadal individuals[J]. Obstet Gynecol, 1977, 49(2): 208-217.
44	HUNTER J D, PIERCE S R, CALIKOGLU A S, et al. Embryonic testicular regression syndrome presenting as primary amenorrhea: a case report and review of disorders of sexual development[J]. J Pediatr Adolesc Gynecol, 2016, 29(4): e59-e62.
45	SULIMA S O, KAMPEN K R, VEREECKE S, et al. Ribosomal lesions promote oncogenic mutagenesis[J]. Cancer Res, 2019, 79(2): 320-327.
46	PAN W A, TSAI H Y, WANG S C, et al. The RNA recognition motif of NIFK is required for rRNA maturation during cell cycle progression[J]. RNA Biol, 2015, 12(3): 255-267.
47	CAPEL B. Vertebrate sex determination: evolutionary plasticity of a fundamental switch[J]. Nat Rev Genet, 2017, 18(11): 675-689.
48	JAMESON S A, LIN Y T, CAPEL B. Testis development requires the repression of Wnt4 by Fgf signaling[J]. Dev Biol, 2012, 370(1): 24-32.
49	BURSAĆ S, BRDOVČAK M C, PFANNKUCHEN M, et al. Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stress[J]. Proc Natl Acad Sci U S A, 2012, 109(50): 20467-20472.
50	YANG K, YANG J, YI J. Nucleolar Stress: hallmarks, sensing mechanism and diseases[J]. Cell Stress, 2018, 2(6): 125-140.

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[2]	黄莹莹, 李嫔. 儿童性发育异常的临床特征及染色体核型分析[J]. , 2013, 33(4): 450-.

DHX37基因在性发育异常中作用的研究进展

Research progress in the role of DHX37 gene in disorders of sex development

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