（本文转自：中华男科学杂志 National Journal of Andrology Zhonghua Nan Ke Xue Za Zhi 2020，26( 9) : 844 － 851）

表 1 常用基因检测技术的比较
Table 1． Comparison of common genetic testing technologies

邓春华( 中山大学附属第一医院)
谷翊群( 国家卫生健康委科学技术研究所)
组 长: 商学军( 南京大学医学院附属金陵医院)
副组长: 李 铮( 上海市第一人民医院)
孙 斐( 南通大学医学院)

杨晓玉( 江苏省人民医院)
刘贵华( 中山大学附属第六医院)
安 淼( 上海交通大学医学院附属仁济医院)

［1］ Inhorn MC，Patrizio P． Infertility around the globe: New thinking on gender，reproductive technologies and global movements in the 21st century． Hum Ｒeprod Update，2015，21( 4) : 411-426．
［2］ Krausz C，Ｒiera-Escamilla A． Genetics of male infertility． Nature reviews． Urology，2018，15( 6) : 369-384．
［3］ Staff A． The Optimal Evaluation of the Infertile Male: AUA Best Practice Statement． 2010．
［4］ Hwang K，Smith JF，Coward ＲM，et al． Evaluation of the azoospermic male: A committee opinion． Fert Steril，2018，109( 5) : 777- 782．
［5］ Medicine PCotASfＲ． Diagnostic evaluation of the infertile male: A committee opinion． Fert Steril，2015，103( 3) : e18-e25．
［6］ Salonia A，Bettocchi C，Carvalho J，et al． EAU Guidelines on sexual and reproductive health． European Association of Urology Guidelines，2020．
［7］ Tahmasbpour E，Balasubramanian D，Agarwal A． A multi-faceted approach to understanding male infertility: Gene mutations，molecular defects and assisted reproductive techniques ( AＲT) ． J Assist Ｒeprod Genet，2014，31( 9) : 1115-1137．
［8］ Vogt PH，Edelmann A，Kirsch S，et al． Human Y chromosome azoospermia factors ( AZF ) mapped to different subregions in Yq11． Hum Mol Genet，1996，5( 7) : 933-943．
［9］ 史轶超，崔英霞，魏 莉，等． 不育男性无精子症因子微缺失 的分子与临床特征: 5 年研究回顾． 中华男科学杂志，2010， 16( 4) : 314-319．
［10］ Krausz C，Hoefsloot L，Simoni M，et al． EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions: State-of-the-art 2013． Andrology，2014，2( 1) : 5-19．
［11］ Tang D，Liu W，Li G，et al． Normal fertility with deletion of sY84 and sY86 in AZFa region． Andrology，2020，8( 2) : 332-336．
［12］ Yatsenko AN，Georgiadis AP，Ｒopke A，et al． X-linked TEX11 mutations，meiotic arrest，and azoospermia in infertile men． N Engl J Med，2015，372( 22) : 2097-2107．
［13］ Krausz C，Ｒiera-Escamilla A，Moreno-Mendoza D，et al． Genetic dissection of spermatogenic arrest through exome analysis: Clinical implications for the management of azoospermic men． Genetics in Medicine，2020．
［14］ Bieth E，Hamdi SM，Mieusset Ｒ． Genetics of the congenital absence of the vas deferens． Hum Genet，2020．
［15］ Chillon M，Casals T，Mercier B，et al． Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens． N Engl J Med，1995，332( 22) : 1475-1480．
［16］ Chen Y，Sun T，Niu Y，et al． Correlations Among Genotype and Outcome in Chinese Male Patients With Congenital Hypogonadotropic Hypogonadism Under HCG Treatment． J Sex Med，2020， 17( 4) : 645-657．
［17］ Yuan P，Liang ZK，Liang H，et al． Expanding the phenotypic and genetic spectrum of Chinese patients with congenital absence of vas deferens bearing CFTＲ and ADGＲG2 alleles． Andrology，2019，7 ( 3) : 329-340．
［18］ Ni WH，Jiang L，Fei QJ，et al． The CFTＲ polymorphisms poly-T， TG-repeats and M470V in Chinese males with congenital bilateral absence of the vas deferens． Asian J Androl，2012，14( 5) : 687- 690．
［19］ Li H，Wen Q，Li H，et al． Mutations in the cystic fibrosis transmembrane conductance regulator ( CFTＲ) in Chinese patients with congenital bilateral absence of vas deferens． J Cyst Fibros，2012， 11( 4) : 316-323．
［20］ Jungwirth A，Diemer T，Kopa Z，et al，EAU Guidelines on Male Infertility． 2019: EAU Guidelines Office．
［21］ Wang H，An M，Liu Y，et al． Genetic diagnosis and sperm retrieval outcomes for Chinese patients with congenital bilateral absence of vas deferens． Andrology，2020．
［22］ Ni WH，Jiang L，Fei QJ，et al． The CFTＲ polymorphisms poly-T， TG-repeats and M470V in Chinese males with congenital bilateral absence of the vas deferens． Asian J Androl，2012，14( 5) : 687- 690．
［23］ Li H，Wen Q，Li H，et al． Mutations in the cystic fibrosis transmembrane conductance regulator ( CFTＲ) in Chinese patients with congenital bilateral absence of vas deferens． J Cyst Fibros，2012， 11( 4) : 316-23．
［24］ Luo S，Feng J，Zhang Y，et al． Mutation analysis of the cystic fibrosis transmembrane conductance regulator gene in Chinese congenital absence of vas deferens patients． Gene，2020: 145045．
［25］ 赵果果，孙红波，郅慧杰，等． CFTＲ 基因 5T 位点多态性与先 天性双侧输精管缺如发病风险相关性研究及 meta 分析． 中华 男科学杂志，2019，25( 03) : 231-237．
［26］ Torra Ｒ，Sarquella J，Calabia J，et al． Prevalence of cysts in seminal tract and abnormal semen parameters in patients with autosomal dominant polycystic kidney disease． Clin J Am Soc Nephrol， 2008，3( 3) : 790-793． ［27］ Torres VE，Harris PC，Pirson Y． Autosomal dominant polycystic kidney disease． Lancet，2007，369( 9569) : 1287-1301．
［28］ Ford WC． Comments on the release of the 5th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen． Asian J Androl，2010，12( 1) : 59-63．
［29］ Escalier D，David G． Pathology of the cytoskeleton of the human sperm flagellum: Axonemal and peri-axonemal anomalies． Biol Cell，1984，50( 1) : 37-52．
［30］ Ben Khelifa M，Coutton C，Zouari Ｒ，et al． Mutations in DNAH1，which encodes an inner arm heavy chain dynein，lead to male infertility from multiple morphological abnormalities of the sperm flagella． Am J Hum Genet，2014，94( 1) : 95-104． ［31］ Takeuchi K，Kitano M，Ishinaga H，et al． Ｒecent advances in primary ciliary dyskinesia． Auris Nasus Larynx，2016，43( 3) : 229- 236．
［32］ Storm van＇s Gravesande K，Omran H． Primary ciliary dyskinesia: Clinical presentation，diagnosis and genetics． Ann Med，2005，37 ( 6) : 439-449．
［33］ Olbrich H，Haffner K，Kispert A，et al． Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry． Nat Genet，2002，30( 2) : 143-144．
［34］ Coutton C，Escoffier J，Martinez G，et al． Teratozoospermia: spotlight on the main genetic actors in the human． Hum Ｒeprod Update，2015，21( 4) : 455-485．
［35］ Tang S，Wang X，Li W，et al． Biallelic Mutations in CFAP43 and CFAP44 Cause Male Infertility with Multiple Morphological Abnormalities of the Sperm Flagella． Am J Hum Genet，2017，100( 6) : 854-864．
［36］ Coutton C，Vargas AS，Amiri-Yekta A，et al． Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in Trypanosoma and human． Nat Commun，2018，9( 1) : 686．
［37］ Baccetti B，Collodel G，Estenoz M，et al． Gene deletions in an infertile man with sperm fibrous sheath dysplasia． Hum Ｒeprod， 2005，20( 10) : 2790-2794．
［38］ Merveille AC，Davis EE，Becker-Heck A，et al． CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs． Nat Genet，2011，43( 1) : 72-78． ［39］ Dong FN，Amiri-Yekta A，Martinez G，et al． Absence of CFAP69 Causes Male Infertility due to Multiple Morphological Abnormalities of the Flagella in Human and Mouse． Am J Hum Genet，2018， 102( 4) : 636-648．
［40］ Li W，He X，Yang S，et al． Biallelic mutations of CFAP251 cause sperm flagellar defects and human male infertility． J Hum Genet，2019，64( 1) : 49-54．
［41］ Sha YW，Xu X，Mei LB，et al． A homozygous CEP135 mutation is associated with multiple morphological abnormalities of the sperm flagella ( MMAF) ． Gene，2017，633: 48-53．
［42］ Martinez G，Kherraf ZE，Zouari Ｒ，et al． Whole-exome sequencing identifies mutations in FSIP2 as a recurrent cause of multiple morphological abnormalities of the sperm flagella． Hum Ｒeprod， 2018，33( 10) : 1973-1984． ［43］ Coutton C，Martinez G，Kherraf ZE，et al． Bi-allelic Mutations in AＲMC2 Lead to Severe Astheno-Teratozoospermia Due to Sperm Flagellum Malformations in Humans and Mice． Am J Hum Genet， 2019，104( 2) : 331-340． ［44］ Shen Y，Zhang F，Li F，et al． Loss-of-function mutations in QＲICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella． Nat Commun，2019，10( 1) : 433．
［45］ Sironen A，Shoemark A，Patel M，et al． Sperm defects in primary ciliary dyskinesia and related causes of male infertility． Cell Mol Life Sci，2020，77( 11) : 2029-2048．
［46］ Merveille AC，Davis EE，Becker-Heck A，et al． CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs． Nat Genet，2011，43( 1) : 72-78． ［47］ Touré A，Martinez G，Kherraf ZE，et al． The genetic architecture of morphological abnormalities of the sperm tail． Hum Genet， 2020．
［48］ Ｒay PF，Toure A，Metzler-Guillemain C，et al． Genetic abnormalities leading to qualitative defects of sperm morphology or function． Clin Genet，2017，91( 2) : 217-232．
［49］ Fellmeth JE，Ghanaim EM，Schindler K． Characterization of macrozoospermia-associated AUＲKC mutations in a mammalian meiotic system． Hum Mol Genet，2016，25( 13) : 2698-2711． ［50］ 李婵娟，张静静，查晓敏，等． 三种畸形精子症的辅助生殖治 疗结局探讨． 中华男科学杂志，2020，26( 8) : 700-707．
［51］ Harbuz Ｒ，Zouari Ｒ，Pierre V，et al． A recurrent deletion of DPY19L2 causes infertility in man by blocking sperm head elongation and acrosome formation． Am J Hum Genet，2011，88 ( 3) : 351-361．
［52］ Chemes HE，Puigdomenech ET，Carizza C，et al． Acephalic spermatozoa and abnormal development of the head-neck attachment: A human syndrome of genetic origin． Hum Ｒeprod，1999，14 ( 7) : 1811-1818．
［53］ Nie H，Tang Y，Qin W． Beyond Acephalic Spermatozoa: The Complexity of Intracytoplasmic Sperm Injection Outcomes． Biomed Ｒes Int，2020，2020: 6279795．
［54］ Zhu F，Wang F，Yang X，et al． Biallelic SUN5 Mutations Cause Autosomal-Ｒecessive Acephalic Spermatozoa Syndrome． Am J Hum Genet，2016，99( 6) : 1405．
［55］ Li L，Sha Y，Wang X，et al． Whole-exome sequencing identified a homozygous BＲDT mutation in a patient with acephalic spermatozoa． Oncotarget，2017，8( 12) : 19914-19922．
［56］ Sha YW，Sha YK，Ji ZY，et al． TSGA10 is a novel candidate gene associated with acephalic spermatozoa． Clin Genet，2018，93 ( 4) : 776-783．
［57］ Pedace L，Laino L，Preziosi N，et al． Longitudinal hormonal evaluation in a patient with disorder of sexual development，46，XY karyotype and one NＲ5A1 mutation． Am J Med Genet A，2014， 164a( 11) : 2938-2946．
［58］ Cools M，Nordenstrm A，Ｒobeva Ｒ，et al． Caring for individuals with a difference of sex development ( DSD) : A Consensus Statement． Nat Ｒev Endocrinol，2018，14( 7) : 415-429．
［59］ Parivesh A，Barseghyan H，Delot E，et al． Translating genomics to the clinical diagnosis of disorders/ differences of sex development． Curr Top Dev Biol，2019，134: 317-375．
［60］ Hughes LA，McKay-Bounford K，Webb EA，et al． Next generation sequencing ( NGS) to improve the diagnosis and management of patients with disorders of sex development ( DSD) ． Endocr Connect，2019，8( 2) : 100-110． ［61］ Ozen S，Onay H，Atik T，et al． Ｒapid Molecular Genetic Diagnosis with Next-Generation Sequencing in 46，XY Disorders of Sex Development Cases: Efficiency and Cost Assessment． Horm Ｒes Paediatr，2017，87( 2) : 81-87．
［62］ Eggers S，Sadedin S，van den Bergen JA，et al． Disorders of sex development: Insights from targeted gene sequencing of a large international patient cohort． Genome Biol，2016，17( 1) : 243．
［63］ Dong Y，Yi Y，Yao H，et al． Targeted next-generation sequencing identification of mutations in patients with disorders of sex development． BMC Med Genet，2016，17: 23． ［64］ Wang H，Zhang L，Wang N，et al． Next-generation sequencing reveals genetic landscape in 46，XY disorders of sexual development patients with variable phenotypes． Hum Genet，2018，137 ( 3) : 265-277．
［65］ Tahmasbpour E，Balasubramanian D，Agarwal A． A multi-facetedapproach to understanding male infertility: Gene mutations，molecular defects and assisted reproductive techniques ( AＲT) ． J Assist Ｒeprod Genet，2014，31( 9) : 1115-1137．
［66］ 中华医学会内分泌学分会性腺学组． 特发性低促性腺激素性 性腺功能减退症诊治专家共识． 中 华 内 科 杂 志，2015，54 ( 8) : 739-744．
［67］ Maione L，Dwyer AA，Francou B，et al． GENETICS IN ENDOCＲINOLOGY: Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: New challenges in the era of oligogenism and next-generation sequencing． Eur J Endocrinol， 2018，178( 3) : Ｒ55-Ｒ80．
［68］ Topaloglu AK． Update on the Genetics of Idiopathic Hypogonadotropic Hypogonadism． J Clin Ｒes Pediatr Endocrinol，2017，9 ( Suppl 2) : 113-122．
［69］ Zhou C，Niu Y，Xu H，et al． Mutation profiles and clinical characteristics of Chinese males with isolated hypogonadotropic hypogonadism． Fertil Steril，2018，110( 3) : 486-495 e5．
［70］ Wambergue C，Zouari Ｒ，Fourati Ben Mustapha S，et al． Patients with multiple morphological abnormalities of the sperm flagella due to DNAH1 mutations have a good prognosis following intracytoplasmic sperm injection． Hum Ｒeprod，2016，31( 6) : 1164-1172．
［71］ Xu H，Li Z，Wang T，et al． Novel homozygous deletion of segmental KAL1 and entire STS cause Kallmann syndrome and Xlinked ichthyosis in a Chinese family． Andrologia，2015，47 ( 10) : 1160-1165．
［72］ Niu Y，Zhou C，Xu H，et al． Novel interstitial deletion in Xp22． 3 in a typical X-linked recessive family with Kallmann syndrome． Andrologia，2018．

(责任编辑：佳学基因)