X-linked isolated growth hormone deficiency: expanding the phenotypic spectrum of SOX3 polyalanine tract expansions.
X-linked isolated growth hormone deficiency: expanding the phenotypic spectrum of SOX3 polyalanine tract expansions.
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DOI：
10.1097/mcd.0b013e32832d06f0
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发表时间：
2009-10
影响因子：
0.7
通讯作者：
Black GC
中科院分区：
文献类型：
--
作者：
Burkitt Wright EM;Perveen R;Clayton PE;Hall CM;Costa T;Procter AM;Giblin CA;Donnai D;Black GC
导致身材矮小的孤立性生长激素（GH）缺乏症（IGHD）的估计出生发病率为4000- 10000分之1（Millar等人，2003），并且通常是散发的，但已知单基因型。已经证明了许多常染色体基因的参与，包括GH-1（Wainrajch等人，1996; Hess等人，2007）、GH释放激素受体（Wainrajch等人，1996）和HESX 1（托马斯等人，2001）基因。由于许多家族性病例的遗传基础尚不清楚，因此进一步提出了分子异质性（Dattani，2005）。X连锁的垂体激素缺乏症以前曾被证明与两个基因座连锁。Xq 21上有一个位点。3-q22与无丙种球蛋白血症有关（Conley等，1991），而另一个与学习障碍和脊柱裂有关，由Xq 26重复引起。1-q27。3（所罗门等人，2002年）。SOX 3位于该复制片段中，并且是在发育中的垂体中表达的SRY相关的高迁移率族盒转录因子（Collignon等人，1996年）。在一个单一的大家庭，Laumonnier等人。（2002）在SOX 3的多聚丙氨酸束中鉴定了编码11个额外丙氨酸的框内33 bp重复，作为与GH缺乏相关的X连锁学习障碍的原因。Woods等人（2005）随后证明，SOX 3中的7个丙氨酸重复可导致先天性垂体功能减退。
Isolated growth hormone (GH) deficiency (IGHD) resulting in short stature has an estimated birth incidence of 1 out of 4000–10 000 (Millar et al., 2003) and is usually sporadic, but monogenic forms are known. Involvement of a number of autosomal genes has been demonstrated, including the GH-1 (Wainrajch et al., 1996; Hess et al., 2007), GH releasing hormone receptor (Wainrajch et al., 1996), and HESX1 (Thomas et al., 2001) genes. Further molecular heterogeneity is suggested, as the inherited basis of many familial cases remains unclear (Dattani, 2005). X-linked combined pituitary hormone deficiency has been demonstrated previously to show linkage to two loci. One locus at Xq21. 3-q22 is associated with agammaglobulinemia (Conley et al., 1991), whereas another is associated with the learning disability and spina bifida and results from duplication of Xq26. 1–q27. 3 (Solomon et al., 2002). SOX3 lies in this duplicated segment, and is an SRY-related high mobility group box transcription factor expressed in the developing pituitary (Collignon et al., 1996). In a single large family, Laumonnier et al.(2002) identified an in-frame 33bp duplication, encoding 11 additional alanines, in the polyalanine tract in SOX3 as the cause for X-linked learning disability associated with GH deficiency. Woods et al.(2005) subsequently demonstrated that a seven alanine repeat duplication in SOX3 could cause congenital hypopituitarism.