Ruiz-Arana Inge-Lore, Hübner Angela, Cetingdag Cigdem, Krude Heiko, Grüters Annette, Fukami Maki, Biebermann Heike, Köhler Birgit
Institute for Experimental Paediatric Endocrinology, Charité, Humboldt University Berlin, Berlin, Germany.
Sex Dev. 2015;9(2):80-5. doi: 10.1159/000371603. Epub 2015 Feb 3.
MAMLD1 is suggested to play a role in the development of 46,XY disorders of sexual development (46,XY DSD). So far, mutations in this gene have been detected in several cases of hypospadias with normal testosterone levels at birth. From in vitro studies it was concluded that Mamld1 might transiently affect testosterone synthesis during genital development. We describe the first MAMLD1 mutation in a 46,XY patient with complete gonadal dysgenesis. The novel MAMLD1 missense mutation (p.P677L) results in a severely reduced transactivation in vitro of the promoter of the MAMLD1 target gene HES3/Hes3. However, as knowledge about the functional role of MAMLD1 in gonadal development is limited, we suggest that additional factors (digenic or oligogenic cause) play a role in the development of complete gonadal dysgenesis in this patient.
MAMLD1被认为在46,XY性发育障碍（46,XY DSD）的发生发展中起作用。到目前为止，在几例出生时睾酮水平正常的尿道下裂病例中检测到了该基因的突变。从体外研究得出的结论是，Mamld1可能在生殖器官发育过程中短暂影响睾酮合成。我们描述了一名患有完全性性腺发育不全的46,XY患者中的首个MAMLD1突变。新的MAMLD1错义突变（p.P677L）导致MAMLD1靶基因HES3/Hes3启动子在体外的反式激活严重降低。然而，由于关于MAMLD1在性腺发育中的功能作用的知识有限，我们认为其他因素（双基因或寡基因原因）在该患者完全性性腺发育不全的发生发展中起作用。
