| Full text | |
| Author(s): Show less - |
da Silva, Thatiana Evilen
[1]
;
Gomes, Nathalia Lisboa
[1]
;
Lerario, Antonio Marcondes
[2, 3]
;
Keegan, Catherine Elizabeth
[4, 5]
;
Nishi, Mirian Yumi
[1]
;
Carvalho, Filomena Marino
[6]
;
Vilain, Eric
[7]
;
Barseghyan, Hayk
[7]
;
Martinez-Aguayo, Alejandro
[8]
;
Forclaz, Maria Veronica
[9]
;
Papazian, Regina
[9]
;
Pedroso de Paula, Leila Cristina
[10]
;
Costa, Eduardo Correa
[10]
;
Carvalho, Luciani Renata
[1]
;
Lima Jorge, Alexander Augusto
[1]
;
Elias, Felipe Martins
[1]
;
Mitchell, Rod
[11]
;
Frade Costa, Elaine Maria
[1]
;
Mendonca, Berenice Bilharinho
[3, 1]
;
Domenice, Sorahia
[1]
Total Authors: 20
|
| Affiliation: Show less - | [1] Univ Sao Paulo, Unidade Endocrinol Desenvolvimento, Lab Hormonios & Genet Mol LIM 42, BR-05403900 Sao Paulo - Brazil
[2] Univ Michigan, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 - USA
[3] Univ Sao Paulo, Fac Med, Lab Sequenciamento Larga Escala, BR-01246903 Sao Paulo - Brazil
[4] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI - USA
[5] Univ Michigan, Sch Med, Dept Pediat Genet, Ann Arbor, MI 48109 - USA
[6] Univ Sao Paulo, Fac Med, Dept Patol, BR-01246903 Sao Paulo - Brazil
[7] Childrens Natl Hlth Syst, Ctr Genet Med Res, Childrens Res Inst, Childrens Natl Med Ctr, Washington, DC 20036 - USA
[8] Pontificia Univ Catolica Chile, Escuela Med, Div Pediat, Santiago 7220436 - Chile
[9] Hosp Nacl Prof Dr A Posadas, Serv Pediat, RA-1684 Buenos Aires, DF - Argentina
[10] Univ Fed Rio Grande do Sul, Programa Atendimento Desordens Desenvolvimento Se, Hosp Clin Porto Alegre, BR-90035903 Porto Alegre, RS - Brazil
[11] MRC, Ctr Reprod Hlth, Queens Med Res Inst, Edinburgh EH16 4TJ, Midlothian - Scotland
Total Affiliations: 11
|
| Document type: | Journal article |
| Source: | JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 104, n. 12, p. 5923-5934, DEC 2019. |
| Web of Science Citations: | 2 |
| Abstract | |
Context: 46,XY Gonadal dysgenesis (GD) is a heterogeneous group of disorders with a wide phenotypic spectrum, including embryonic testicular regression syndrome (ETRS). Objective: To report a gene for 46,XY GD etiology, especially for ETRS. Design: Screening of familial cases of 46,XY GD using whole-exome sequencing and sporadic cases by target gene-panel sequencing. Setting: Tertiary Referral Center for differences/disorders of sex development (DSD). Patients and Interventions: We selected 87 patients with 46,XY DSD (17 familial cases from 8 unrelated families and 70 sporadic cases); 55 patients had GD (among them, 10 patients from 5 families and 8 sporadic cases had ETRS), and 32 patients had 46,XY DSD of unknown etiology. Results: We identified four heterozygous missense rare variants, classified as pathogenic or likely pathogenic in the Asp-Glu-Ala-His-box (DHX) helicase 37 (DHX37) gene in five families (n = 11 patients) and in six sporadic cases. Two variants were recurrent: p.Arg308Gln (in two families and in three sporadic cases) and p.Arg674Trp (in two families and in two sporadic cases). The variants were specifically associated with ETRS (7/14 index cases; 50%). The frequency of rare, predicted-to-be-deleterious DHX37 variants in this cohort (14%) is significantly higher than that observed in the Genome Aggregation Database (0.4%; P < 0.001). Immunohistochemistry analysis in human testis showed that DHX37 is mainly expressed in germ cells at different stages of testis maturation, in Leydig cells, and rarely in Sertoli cells. Conclusion: This strong genetic evidence identifies DHX37 as a player in the complex cascade of male gonadal differentiation and maintenance. (AU) | |
| FAPESP's process: | 13/02162-8 - Molecular pathogenesis and characterization of monogenic developmental diseases: a route to translational medicine |
| Grantee: | Berenice Bilharinho de Mendonça |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 05/04726-0 - Molecular characterization of congenital endocrine diseases that affect growth and development |
| Grantee: | Ana Claudia Latronico Xavier |
| Support Opportunities: | Research Projects - Thematic Grants |