Sukumaran Anju, Desmangles Jean-Claude, Gartner Lou Ann, Buchlis John
J Pediatr Endocrinol Metab. 2013;26(7-8):775-9. doi: 10.1515/jpem-2012-0354.
The sex chromosome composition of the primordial gonad, either 46XX or 46XY, determines its differentiation as ovaries or testes. Local hormones secreted by developing gonads and tissue specific transcription factors influence the differentiation of external and internal genital structures. Dosage sensitive sex reversal adrenal hypoplasia congenita critical region (DAX1) on Xp21 is a gene which is expressed in the developing adrenals, gonads, hypothalamus and pituitary gland. Duplication of this area causes dosage sensitive male-to-female sex reversal while mutation or deletion leads to adrenal hypoplasia congenita with hypogonadotropic hypogonadism in affected males.
To report a case with duplication of the X chromosome segment within the region of Xp21.1-22.2 resulting in 46 XY sex reversal and a literature review on DAX1 and dosage sensitive sex reversal (DSS).
We present the clinical history, physical findings, laboratory, and imaging study results in a newborn baby. This infant was sex assigned as female at birth and had normal female external genitalia. Chromosome analysis was done due to multiple minor malformations and showed a karyotype of 46 Xp+Y. Fluorescent in situ hybridization analysis revealed the duplication in the DSS area.
Duplication of the DAX1 gene on the X chromosome with normal sex determining region of Y (SRY) results in 46 XY sex reversal. This was inherited from the mother who had normal ovarian function. Additional problems include growth failure, mental retardation and multiple congenital anomalies. The baby did not have a mutation or deletion of DAX1, which would have caused adrenal insufficiency and hypogonadism.
原始性腺的性染色体组成，即46XX或46XY，决定了其向卵巢或睾丸的分化。发育中的性腺分泌的局部激素和组织特异性转录因子影响外生殖器和内生殖器结构的分化。位于Xp21的剂量敏感性性别反转先天性肾上腺发育不全关键区域（DAX1）是一个在发育中的肾上腺、性腺、下丘脑和垂体中表达的基因。该区域的重复会导致剂量敏感性男性向女性的性别反转，而突变或缺失则会导致受影响男性出现先天性肾上腺发育不全伴低促性腺激素性性腺功能减退。
报告一例Xp21.1 - 22.2区域内X染色体片段重复导致46 XY性别反转的病例，并对DAX1和剂量敏感性性别反转（DSS）进行文献综述。
我们呈现了一名新生儿的临床病史、体格检查结果、实验室检查和影像学研究结果。该婴儿出生时被判定为女性，具有正常的女性外生殖器。由于多种轻微畸形进行了染色体分析，结果显示核型为46 Xp + Y。荧光原位杂交分析显示在DSS区域存在重复。
X染色体上DAX1基因的重复以及Y染色体正常的性别决定区域（SRY）导致了46 XY性别反转。这是从卵巢功能正常的母亲遗传而来。其他问题包括生长发育迟缓、智力障碍和多种先天性异常。该婴儿没有DAX1的突变或缺失，否则会导致肾上腺功能不全和性腺功能减退。
