دورية أكاديمية
Molecular diagnostics of disorders of sexual development: an Indian survey and systems biology perspective.
| العنوان: | Molecular diagnostics of disorders of sexual development: an Indian survey and systems biology perspective. |
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| المؤلفون: | Nagaraja MR; a Department of Biochemistry , Akash Institute of Medical Sciences & Research Centre , Bangalore , India., Gubbala SP; b Division of Pharmacology and Toxicology , CSIR- Indian Institute of Chemical Technology , Hyderabad , India., Delphine Silvia CRW; a Department of Biochemistry , Akash Institute of Medical Sciences & Research Centre , Bangalore , India., Amanchy R; b Division of Pharmacology and Toxicology , CSIR- Indian Institute of Chemical Technology , Hyderabad , India. |
| المصدر: | Systems biology in reproductive medicine [Syst Biol Reprod Med] 2019 Apr; Vol. 65 (2), pp. 105-120. Date of Electronic Publication: 2018 Dec 14. |
| نوع المنشور: | Journal Article; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Informa Healthcare Country of Publication: England NLM ID: 101464963 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-6376 (Electronic) Linking ISSN: 19396368 NLM ISO Abbreviation: Syst Biol Reprod Med |
| أسماء مطبوعة: | Publication: London : Informa Healthcare Original Publication: New York : Informa Healthcare |
| مواضيع طبية MeSH: | Systems Biology*, Disorders of Sex Development/*diagnosis , Disorders of Sex Development/*genetics, Disorders of Sex Development/epidemiology ; Female ; Humans ; India/epidemiology ; Male ; Mutation ; Surveys and Questionnaires |
| مستخلص: | We aimed to survey the monogenic causes of disorders of sex development (DSD) and thereby its prevalence in India. This study revealed mutations resulting in androgen insensitivity syndrome, 5α-reductase type 2 deficiency, and gonadal dysgenesis were commonly reported. Intriguingly, AR deficits were the most prevalent (32 mutations) and of 11/26 missense mutations were in exons 4-8 (encoding ligand binding domain). The unique features of SRD5A2 defects were p.R246Q (most prevalent) and p.G196S could be mutational hotspots, dual gene defects (p.A596T in AR and p.G196S in SRD5A2) in a patient with hypospadias and novel 8 nucleotide deletion (exon 1) found in a patient with perineal hypospadias. Deficits in SRY, WT1, DHH, NR5A1, and DMRT1 caused 46,XY gonadal dysgenesis. Notably, mutations in AR, SRD5A2, MAMLD1, WT1, and MAP3K1 have led to hypospadias and only one CYP19A1 mutation caused aromatase deficiency was reported to date. Data mining from various databases has not only reinforced the role of well-established genes (e.g., SRY, WT1, DHH, NR5A1, DMRT1, AR, SRD5A2, MAMLD1) involved in DSD but also provided us 12 more potential candidate genes (ACVR1, AMHR2, CTNNB1, CYP11A1, CYP19A1, FGFR2, FGF9, PRKACA, PRKACG, SMAD9, TERT, ZFPM2), which benefit from a close association with the well-established genes involved in DSD and might be useful to screen owing to their direct gene-phenotype relationship or through direct functional interaction. As more genes have been revealed in relation to DSD, we believe ultimately it holds a better scenario for therapeutic regimen. Despite the advances in translational medicine, hospitals are yet to adopt genetic testing and counseling facilities in India that shall have potential impact on clinical diagnosis. Abbreviations: 5α-RD2: 5α-Reductase type 2; AIS: androgen insensitivity syndrome; AMH: antimullerian hormone; AMHR: antimullerian hormone receptor; AR: androgen receptor gene; CAH: congenital adrenal hyperplasia; CAIS: complete AIS; CAH: congenital adrenal hyperplasia; CHH: congenital hypogonadotropic hypogonadism; CXORF6: chromosome X open reading frame 6 gene; CYP19A1: cytochrome P450 family 19 subfamily A member 1 gene; DHT: dihydrotestosterone; DMRT1: double sex and mab-3 related transcription factor 1 gene; DSD: disorders of sexual development; GD: gonadal dysgenesis; HGMD: human gene mutation database; IH: isolated hypospadias; MAMLD1: mastermind like domain containing 1 gene; MIS: mullerian inhibiting substance; NTD: N-terminal domain; OT DSD: ovotesticular DSD; PAIS: partial AIS; SOX9: SRY-related HMG-box 9 gene; SRY: sex-determining region Y gene; STAR: steroidogenic acute regulatory protein gene; SRD5A2: steroid 5 alpha-reductase 2 gene; T DSD: testicular DSD; T: testosterone; WNT4: Wnt family member 4 gene; WT1: Wilms tumor 1 gene; Δ |
| فهرسة مساهمة: | Keywords: DSD; androgen insensitivity; hypospadias; reproductive systems biology |
| تواريخ الأحداث: | Date Created: 20181215 Date Completed: 20190730 Latest Revision: 20190730 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1080/19396368.2018.1549619 |
| PMID: | 30550360 |
| قاعدة البيانات: | MEDLINE |
PDF full text from Publisher | تدمد: | 1939-6376 |
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| DOI: | 10.1080/19396368.2018.1549619 |