Next-generation DNA sequencing in an appropriate sex assignment: Case report of two phenotypically similar patients with 46, XY disorder of sex development.
Authors: Irina L Nikitina, Elena K Kudryashova, Ruslan R Batrutdinov, Anna A Kostareva, Igor A Kelmanson, Elena N Grineva
Background. Disorders of sex development (DSD) are known as the inborn atypical development of chromosomal, gonadal, or anatomic sex. New opportunities in counseling DSD patients have emerged with an advent of the next generation DNA sequencing (NGS) techniques. Case presentation. Two clinical 46, XY DSD cases having similar phenotypical features, including ambiguous genitalia, are presented in this paper. In the first patient, no causative variant was found, meanwhile, a heterozygous variant in the CHD 7 gene considered as likely-benign was identified (chr8:61693942, rs377139749, NM_017780.3:c.2053_2058dupGCAAAA p.Lys686_Thr687insAlaLys). Neither gonadal ability to produce androgens, nor tissue androgen sensitivity was impaired, therefore leading to a decision to maintain the initially assigned male sex in this patient. In the other patient, the study revealed previously reported heterozygous missense variant in the SEMA3A gene (chr7:83636785, rs769957117, NM_006080.2:c.А1024G:p.Met342Val) responsible for HH type 16 (OMIM 614897). As well, a novel hemizygous variant in the AR gene (chrX:66942818, AR:NM_000044:c.G2599C:p.Val867Leu) was identified. In conjunction with the features of HH, this leads to a decision to reassign the sex of rearing to a female. Conclusion. NGS technique may be helpful in optimal sex assignment in DSD cases.
Keywords: case report, disorders of sex development, next-generation sequencing, genes, genital ambiguity, gene variants
Authors
Elena K Kudryashova
Pediatric Endocrinology Laboratory, Institute of Pediatric Endocrinology of the V.A. Almazov National Medical Research Centre, Russia
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Pubmed Articles
Correspondence to:
Irina L Nikitina, Department of Children's Diseases, Institute for Medical Education of the VAAlmazov National Medical Research Centre, Russia nikitina0901@gmail.com
Publication history:
Received 17 Nov 2018
Revised 08 Mar 2019
Accepted 20 Mar 2019
Published online 25 Apr 2019
Published in print 29 May 2019
Nikitina IL, Kudryashova EK, Batrutdinov RR, Kostareva AA, Kelmanson IA, Grineva EN. Next-generation DNA sequencing in an appropriate sex assignment: Case report of two phenotypically similar patients with 46, XY disorder of sex development.. EJMCR. 2019; 3(2): 68-73. doi:
10.24911/ejmcr/173-1542301068
Nikitina IL, Kudryashova EK, Batrutdinov RR, Kostareva AA, Kelmanson IA, Grineva EN. Next-generation DNA sequencing in an appropriate sex assignment: Case report of two phenotypically similar patients with 46, XY disorder of sex development.. https://www.ejmcr.com/?mno=17382 [Access: March 29, 2024]. doi:
10.24911/ejmcr/173-1542301068
Nikitina IL, Kudryashova EK, Batrutdinov RR, Kostareva AA, Kelmanson IA, Grineva EN. Next-generation DNA sequencing in an appropriate sex assignment: Case report of two phenotypically similar patients with 46, XY disorder of sex development.. EJMCR. 2019; 3(2): 68-73. doi:
10.24911/ejmcr/173-1542301068
Nikitina IL, Kudryashova EK, Batrutdinov RR, Kostareva AA, Kelmanson IA, Grineva EN. Next-generation DNA sequencing in an appropriate sex assignment: Case report of two phenotypically similar patients with 46, XY disorder of sex development.. EJMCR. (2019), [cited March 29, 2024]; 3(2): 68-73. doi:
10.24911/ejmcr/173-1542301068
Nikitina, I. L., Kudryashova, . E. K., Batrutdinov, . R. R., Kostareva, . A. A., Kelmanson, . I. A. & Grineva, . E. N. (2019) Next-generation DNA sequencing in an appropriate sex assignment: Case report of two phenotypically similar patients with 46, XY disorder of sex development.. EJMCR, 3 (2), 68-73. doi:
10.24911/ejmcr/173-1542301068
Nikitina, Irina L, Elena K Kudryashova, Ruslan R Batrutdinov, Anna A Kostareva, Igor A. Kelmanson, and Elena N. Grineva. 2019. Next-generation DNA sequencing in an appropriate sex assignment: Case report of two phenotypically similar patients with 46, XY disorder of sex development.. European Journal of Medical Case Reports, 3 (2), 68-73. doi:
10.24911/ejmcr/173-1542301068
Nikitina, Irina L, Elena K Kudryashova, Ruslan R Batrutdinov, Anna A Kostareva, Igor A. Kelmanson, and Elena N. Grineva. "Next-generation DNA sequencing in an appropriate sex assignment: Case report of two phenotypically similar patients with 46, XY disorder of sex development.." European Journal of Medical Case Reports 3 (2019), 68-73. doi:
10.24911/ejmcr/173-1542301068
Nikitina, Irina L, Elena K Kudryashova, Ruslan R Batrutdinov, Anna A Kostareva, Igor A. Kelmanson, and Elena N. Grineva. "Next-generation DNA sequencing in an appropriate sex assignment: Case report of two phenotypically similar patients with 46, XY disorder of sex development.." European Journal of Medical Case Reports 3.2 (2019), 68-73. Print. doi:
10.24911/ejmcr/173-1542301068
Nikitina, I. L., Kudryashova, . E. K., Batrutdinov, . R. R., Kostareva, . A. A., Kelmanson, . I. A. & Grineva, . E. N. (2019) Next-generation DNA sequencing in an appropriate sex assignment: Case report of two phenotypically similar patients with 46, XY disorder of sex development.. European Journal of Medical Case Reports, 3 (2), 68-73. doi:
10.24911/ejmcr/173-1542301068