Mutation Analysis of the SRY Gene in a Patient with Turner Syndrome

Testis-determining factor (TDF) is an alternative term for the sex-determining region (SRY) gene found on the Y chromosome. SRY gene mutations can cause a wide range of sex development issues. The single-exon SRY gene is a short and intronless sex-determining gene with a DNA-binding high mobility group (HMG) box that is highly conserved. We performed cytogenetic analysis on one patient with Turner syndrome having a 45,X/46,XY chromosomal composition. Further, we used polymerase chain reaction, single-stranded conformational polymorphism, and automated DNA sequencing to detect a substitution of C→A (missense mutation) at codon 139, which led to an amino acid shift from Proline to Glutamine (P139Q) outside but downstream of the HMG box in the SRY gene. No further alterations in the SRY gene were discovered in the patient. The absence of one X chromosome in 88% of the patient’s cells might have resulted in a wide variety of phenotypic complications.

[1]  Lisal J. Folsom,et al.  Reproductive Issues in Women with Turner Syndrome. , 2015, Endocrinology and metabolism clinics of North America.

[2]  S. Gimelli,et al.  Identification and molecular modelling of a novel familial mutation in the SRY gene implicated in the pure gonadal dysgenesis , 2007, European Journal of Human Genetics.

[3]  S. Husain,et al.  Three new novel point mutations localized within and downstream of high-mobility group-box region in SRY gene in three Indian females with Turner syndrome. , 2005, The Journal of clinical endocrinology and metabolism.

[4]  L. Castaño,et al.  A novel postzygotic nonsense mutation in SRY in familial XY gonadal dysgenesis , 1996, Human Genetics.

[5]  S. Batra,et al.  Two new novel point mutations localized upstream and downstream of the HMG box region of the SRY gene in three Indian 46,XY females with sex reversal and gonadal tumour formation. , 2004, Molecular human reproduction.

[6]  P. Stenson,et al.  Human Gene Mutation Database (HGMD®): 2003 update , 2003, Human mutation.

[7]  M. de Mello,et al.  Novel mutations affecting SRY DNA-binding activity: the HMG box N65H associated with 46,XY pure gonadal dysgenesis and the familial non-HMG box R30I associated with variable phenotypes , 2002, Journal of Molecular Medicine.

[8]  P. Koopman,et al.  Matching SOX: partner proteins and co-factors of the SOX family of transcriptional regulators. , 2002, Current opinion in genetics & development.

[9]  E. Pásaro,et al.  A point mutation, R59G, within the HMG-SRY box in a female 45,X/46,X, psu dic(Y)(pter→q11::q11→pter) , 2002, Human Genetics.

[10]  R. Sokol.  Infertility in men with cystic fibrosis. , 2001, Current opinion in pulmonary medicine.

[11]  P. Canto,et al.  A mutation in the 5' non-high mobility group box region of the SRY gene in patients with Turner syndrome and Y mosaicism. , 2000, The Journal of clinical endocrinology and metabolism.

[12]  B. Capel,et al.  The battle of the sexes , 2000, Mechanisms of Development.

[13]  M. Fellous,et al.  Sex determination and the Y chromosome. , 1999, American journal of medical genetics.

[14]  Yun-Fai Chris Lau,et al.  Gonadoblastoma, testicular and prostate cancers, and the TSPY gene. , 1999, American journal of human genetics.

[15]  D. Warburton,et al.  A de novo mutation (Gln2Stop) at the 5' end of the SRY gene leads to sex reversal with partial ovarian function. , 1998, American journal of human genetics.

[16]  A. Sinclair,et al.  Mutations in SRY and SOX9: Testis‐determining genes , 1997, Human mutation.

[17]  K. Jones,et al.  Smith's Recognizable Patterns of Human Malformation , 1996 .

[18]  A. Gronenborn,et al.  NMR spectroscopic analysis of the DNA conformation induced by the human testis determining factor SRY. , 1995, Biochemistry.

[19]  P. Beer-Romero,et al.  Evidence that the SRY protein is encoded by a single exon on the human Y chromosome. , 1993, Genomics.

[20]  M. Ferguson-Smith,et al.  Analysis of the SRY gene in 22 sex-reversed XY females identifies four new point mutations in the conserved DNA binding domain. , 1993, Human molecular genetics.

[21]  E. Vilain,et al.  XY sex reversal associated with a deletion 5' to the SRY "HMG box" in the testis-determining region. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[22]  P N Goodfellow,et al.  DNA binding activity of recombinant SRY from normal males and XY females. , 1992, Science.

[23]  Peter Goodfellow,et al.  "Male Development of Chromosomally Female Mice Transgenic for Sry gene" (1991), by Peter Koopman, et al. , 2014 .

[24]  Robin Lovell-Badge,et al.  A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif , 1990, Nature.

[25]  D. Page,et al.  Hypothesis: a Y-chromosomal gene causes gonadoblastoma in dysgenetic gonads. , 1987, Development.

[26]  A. Knudson.  Mutation and cancer: statistical study of retinoblastoma. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[27]  R. Scully.  Gonadoblastoma. A review of 74 cases , 1970, Cancer.