Molecular diagnostics of disorders of sexual development: an Indian survey and systems biology perspective.

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; Δ4: androstenedione.

Palmar dermatoglyphics in carcinoma breast of Indian women.

The present study was planned to assess the relationship of palmar dermatoglyphic patterns of hands in women with breast cancer and or at risk for developing breast cancer. This study was conducted on 100 histopathologically confirmed breast cancer patients in women and their digital dermatoglyphic patterns were studied to assess their association with the type and onset of breast cancer. Simultaneously 100 age-matched controls were also selected with no self or familial history of a diagnosed breast cancer and the observations were recorded. The differences of qualitative (dermatoglyphic patterns) data were tested for their significance using the chi-square test, and Student's t-test was used for quantitative (ridge counts and pattern intensity index) data analysis. The results of the study indicated statistically significant changes in finger ridge count and fingertip pattern in cases of carcinoma breast as compared to the control group. Palmar dermatoglyphics is simple, inexpensive, anatomical and non-invasive and may be used as a reliable indicator for screening of high-risk population in developing country like India, for early detection and early therapy, thus reducing the morbidity and mortality in cases of carcinoma breast.