scholarly journals Sex-Determining Gene(s) on Distal 9p: Clinical and Molecular Studies in Six Cases*

2000 ◽  
Vol 85 (9) ◽  
pp. 3094-3100 ◽  
Author(s):  
Koji Muroya ◽  
Torayuki Okuyama ◽  
Keiji Goishi ◽  
Yoshifumi Ogiso ◽  
Shin Fukuda ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
External Genitalia ◽  
Chromosome 9 ◽  
Severe Malnutrition ◽  
Female Case ◽  
Dm Domain ◽  
Baseline Values ◽  
Male External Genitalia ◽  
Female External Genitalia

Abstract We report on clinical and molecular findings in five karyotypic males (cases 1–5) and one karyotypic female (case 6) with distal 9p monosomy. Cases 1–3 and 6 had female external genitalia, case 4 showed ambiguous external genitalia, and case 5 exhibited male external genitalia with left cryptorchidism and right intrascrotal testis. Gonadal explorations at gonadectomy in cases 3 and 4 revealed that case 3 had left streak gonad and right agonadism, and case 4 had bilateral hypoplastic testes. Endocrine studies in cases 1–4 and 6 showed that cases 1, 3, and 6 had definite primary hypogonadism, with basal FSH levels of 54, 39, and 41 IU/L, respectively, whereas case 2 with severe malnutrition was unremarkable for the baseline values, and case 4 had fairly good testicular function. Fluorescence in situ hybridization and microsatellite analyses demonstrated that all cases had hemizygosity of the 9p sex-determining region distal to D9S1779, with loss of the candidate sex-determining genes DMRT1 and DMRT2 from the abnormal chromosome 9. Sequence analysis in cases 1–4 and 6 showed that they had normal sequences of each exon of DMRT1 and the DM domain of DMRT2 on the normal chromosome 9, and that cases 1–4 had normal SRY sequence. The results provide further support for the presence of a sex-determining gene(s) on distal 9p and favor the possibility of DMRT1 and/or DMRT2 being the sex-determining gene(s). Furthermore, as hemizygosity of the 9p sex-determining region was associated with a wide spectrum of gonadogenesis from agonadism to testis formation in karyotypic males and with primary hypogonadism regardless of karyotypic sex, it is inferred that haploinsufficiency of the 9p sex-determining gene(s) primarily hinders the formation of indifferent gonad, leading to various degrees of defective testis formation in karyotypic males and impaired ovary formation in karyotypic females.

scholarly journals Chromosome Y as A Marker for Sex Discrepancies in Patients With Organ Transplants: A Case Report

2020 ◽  
Author(s):  
Nuria Balaguer ◽  
Emilia Mateu-Brull ◽  
Roy Pascal Naja ◽  
Jara Ben Nagi ◽  
Miguel Milán
Keyword(s):  
Scientific Literature ◽  
External Genitalia ◽  
Marrow Transplant ◽  
Organ Transplants ◽  
Ultrasound Scan ◽  
Structural Alterations ◽  
Free Dna ◽  
Male Donor ◽  
Female External Genitalia

Abstract Background: Organ transplantations cause discrepancy in results from cell-free DNA (cfDNA) testing, but scientific literature is scarce.Case: A 33-year old gravida underwent cfDNA testing, which showed high levels of Y chromosome (ChrY) in the maternal bloodstream. The ChrY pattern was comparable to an adult male reference. As a result, cfDNA testing was only informative for autosomes. Routine 20-week ultrasound scan showed no structural alterations and the presence of female external genitalia. Post-clinical research revealed that the patient received a bone marrow transplant from a male donor several years before. Fluorescence in situ hybridization showed that 100% of nuclei analysed from the patient’s lymphocytes presented a ChrY.Conclusion: This case demonstrates ChrY can be used as a marker to avoid sex discrepancies in certain patients with organ transplants.

scholarly journals Chromosome Y as a marker for sex discrepancies in patients with organ transplants: a case report

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Nuria Balaguer ◽  
Emilia Mateu-Brull ◽  
Roy P. Naja ◽  
Jara B. Nagi ◽  
Miguel Milán
Keyword(s):  
Scientific Literature ◽  
External Genitalia ◽  
Marrow Transplant ◽  
Organ Transplants ◽  
Ultrasound Scan ◽  
Structural Alterations ◽  
Free Dna ◽  
Male Donor ◽  
Female External Genitalia

Abstract Background Organ transplantations cause discrepancy in results from cell-free DNA (cfDNA) testing, but scientific literature is scarce. Case A 33-year old gravida underwent cfDNA testing, which showed high levels of Y chromosome (ChrY) in the maternal bloodstream. The ChrY pattern was comparable to an adult male reference. As a result, cfDNA testing was only informative for autosomes. Routine 20-week ultrasound scan showed no structural alterations and the presence of female external genitalia. Post-clinical research revealed that the patient received a bone marrow transplant from a male donor several years before. Fluorescence in situ hybridization showed that 100% of nuclei analysed from the patient’s lymphocytes presented a ChrY. Conclusion This case demonstrates ChrY can be used as a marker to avoid sex discrepancies in certain patients with organ transplants.

scholarly journals Normal male external genitalia do not rule out CYP11A1 deficiency

2019 ◽  
Vol 12 (7) ◽  
pp. e228235
Author(s):  
Vijaya Sarathi ◽  
Chithambaram Nagalingam
Keyword(s):  
Adrenal Insufficiency ◽  
External Genitalia ◽  
Serum Cortisol ◽  
Normal Male ◽  
Sequencing Analysis ◽  
Primary Adrenal Insufficiency ◽  
First Case ◽  
Renin Level ◽  
Male External Genitalia ◽  
Female External Genitalia

Defects in the initial steps of steroidogenesis usually present with female external genitalia in both 46,XX and 46,XY. Hence, they are not often considered in the differential diagnosis of primary adrenal insufficiency children with normal male external genitalia. Here, we report a boy with normal male external genitalia who presented with hyperpigmentation since the age of 2 years but diagnosis was delayed till 11 years of age. Evaluation revealed low-serum cortisol with elevated adrenocorticotropic hormone and direct renin level confirming primary adrenal insufficiency. Clinical exome sequencing analysis revealed a homozygous c.1351C>T (p.R451W) mutation in exon 8 of the CYP11A1 gene which was confirmed on Sanger sequencing. Both parents were heterozygous for the variation. To conclude, we report the first case of CYP11A1 deficiency from India. The report reiterates the existence of non-classic CYP11A1 deficiency characterised by primary adrenal insufficiency and normal male external genitalia in 46,XY.

Cytogenetics and sex determination in man and mammals

1970 ◽  
Vol 2 (S2) ◽  
pp. 7-30 ◽  
Author(s):  
C. E. Ford
Keyword(s):  
Y Chromosome ◽  
External Genitalia ◽  
Mutant Gene ◽  
Normal Female ◽  
Human Female ◽  
Present Evidence ◽  
Male Development ◽  
Sex Development ◽  
Internal Genitalia ◽  
Male External Genitalia

SummarySex in man and probably throughout the class mammalia is normally determined by the presence of a Y chromosome (male) or its absence (female). The presence of genetic loci on both the long and the short arm of the X chromosome in double dose appears to be essential for the development of mature functional ovaries in the human female though a single X suffices in the female mouse.The development of masculine genital anatomy and phenotype is a consequence of prior formation of testes. In the absence of gonads of either kind, female internal and external genitalia are formed but secondary sex development fails. In rare human families a mutant gene suppresses the development of male external genitalia in 46, XY embryos but permits the development of testes and male internal genitalia. The external phenotype is normal female (syndrome of testicular feminization). A sex-linked mutant gene in the mouse has a similar effect.The locus or loci directly concerned with male development might lie wholly on the Y chromosome or might be located on another chromosome or chromosomes. In the latter case it (or they) must be repressed in the female and normally activated by a locus or loci on the Y chromosome in the male. Present evidence does not permit the exclusion of either possibility.

scholarly journals The Role of Sonic Hedgehog-Gli2 Pathway in the Masculinization of External Genitalia

Endocrinology ◽  
2011 ◽  
Vol 152 (7) ◽  
pp. 2894-2903 ◽  
Author(s):  
Shinichi Miyagawa ◽  
Daisuke Matsumaru ◽  
Aki Murashima ◽  
Akiko Omori ◽  
Yoshihiko Satoh ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
External Genitalia ◽  
Sexually Dimorphic ◽  
Hedgehog Signaling Pathway ◽  
Initial Development ◽  
Urethral Plate ◽  
Male External Genitalia

During embryogenesis, sexually dimorphic organogenesis is achieved by hormones produced in the gonad. The external genitalia develop from a single primordium, the genital tubercle, and their masculinization processes depend on the androgen signaling. In addition to such hormonal signaling, the involvement of nongonadal and locally produced masculinization factors has been unclear. To elucidate the mechanisms of the sexually dimorphic development of the external genitalia, series of conditional mutant mouse analyses were performed using several mutant alleles, particularly focusing on the role of hedgehog signaling pathway in this manuscript. We demonstrate that hedgehog pathway is indispensable for the establishment of male external genitalia characteristics. Sonic hedgehog is expressed in the urethral plate epithelium, and its signal is mediated through glioblastoma 2 (Gli2) in the mesenchyme. The expression level of the sexually dimorphic genes is decreased in the glioblastoma 2 mutant embryos, suggesting that hedgehog signal is likely to facilitate the masculinization processes by affecting the androgen responsiveness. In addition, a conditional mutation of Sonic hedgehog at the sexual differentiation stage leads to abnormal male external genitalia development. The current study identified hedgehog signaling pathway as a key factor not only for initial development but also for sexually dimorphic development of the external genitalia in coordination with androgen signaling.

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