一种新的X连锁智力障碍（XLMR）综合征伴迟发性原发性睾丸功能衰竭、身材矮小和小头畸形定位于Xq25-q26

摘要(中文译文)

X连锁智力障碍（XLMR）是一种异质性疾病，既有综合征型，也有非综合征型。本文报道了一个综合征型XLMR家系的临床和分子特征，该家系还伴有性腺功能减退和身材矮小。我们研究了一个家系，其中两代共四名男性成员表现为高促性腺激素性性腺功能减退，并伴有睾丸小且异常。其中两名男性出现了迟发性睾丸上升。此外，所有受累男性均有身材矮小（低于第0.4百分位）和轻度学习困难，四名中有三名为小头畸形。核型正常，内分泌检查证实为原发性睾丸功能衰竭。该表型以X连锁性状分离。利用22个微卫星标记进行单倍型和遗传两点连锁分析，排除了整条X染色体，仅保留Xq25-Xq27区域，涵盖13.7Mb，在θ=0.05时标记DXS8038的最大LOD评分为1.1。此前报道的一个伴有性腺功能减退和身材矮小的XLMR家系定位于与本家系相同的X染色体区域。然而，该另一家系中描述的更为严重的智力障碍、肌肉萎缩和震颤提示，本家系可能患有一种新的XLMR综合征。

Abstract

X-linked mental retardation (XLMR) is a heterogeneous disorder with both syndromic and non-syndromic forms. Here we describe the clinical and molecular characterisation of a family with a syndromic form of XLMR with hypogonadism and short stature. We investigated a family in which four male members in two generations presented with hypergonadotrophic hypogonadism associated with development of small and abnormal testes. In two of the males, late-onset testicular ascent was noted. In addition, all affected males had short stature (<0.4th centile) and mild learning difficulties and three out of the four had microcephaly. Karyotypes were normal and endocrine investigations confirmed primary testicular failure. The phenotype segregated as an X-linked trait. Haplotype and genetic two-point linkage analysis with 22 microsatellites excluded the whole X chromosome except for a region on Xq25-Xq27 encompassing 13.7Mb with a maximum LOD score of 1.1 for marker DXS8038 at theta=0.05. One family previously described as having XLMR with hypogonadism and short stature maps to the same X chromosome region implicated in our family. However, the more severe mental retardation, muscle wasting and tremor described in this other family would suggest that our family is affected by a novel XLMR syndrome.

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