Clinical and pathologic correlations in genetically distinct forms of atrichia.
Clinical and pathologic correlations in genetically distinct forms of atrichia.
复制标题
DOI：
10.1001/archderm.139.12.1591
复制
发表时间：
2003-12
影响因子：
--
通讯作者：
A. Zlotogorski;Z. Hochberg;P. Mirmirani;A. Metzker;D. Ben-Amitai;A. Martinez-Mir;A. Panteleyev;A. Christiano
中科院分区：
文献类型：
--
作者：
A. Zlotogorski;Z. Hochberg;P. Mirmirani;A. Metzker;D. Ben-Amitai;A. Martinez-Mir;A. Panteleyev;A. Christiano
背景最近在分子水平上定义了两种不同类型的丘疹闭锁的遗传学基础。在有丘疹病变的闭锁中，最近发现了染色体8p21上无毛基因的突变。在维生素D依赖型IIA型(VDDR IIA；OMIM 277440)的临床环境中也会出现丘疹便秘，这是由于染色体12q12-q14上的维生素D受体基因突变引起的。尽管这两种类型的闭锁有不同的遗传基础，但临床表现惊人地相似，并显示出这种表型特有的经典病原学特征。我们试图记录APL和VDDR IIA的临床和分子特征。对来自3个APL家系和2个VDDR IIA家系的先证者和家系成员的基因组DNA进行了无毛和维生素D受体基因的分子分析。我们对APL和VDDR IIA患者的闭锁进行了临床和组织学比较，并通过鉴定致病突变强调了闭锁的遗传异质性基础。结论提高对这些疾病的认识将有助于对VDDR IIA中的软骨病进行早期诊断和潜在的治疗干预，避免APL和VDDR IIA中的软骨病的治疗。它们的表型相似性提示HR和VDR之间可能存在功能关系。
BACKGROUND The genetic basis of 2 distinct forms of atrichia with papules has recently been defined at the molecular level. In atrichia with papular lesions (APL; Online Mendelian Inheritance in Man [OMIM] 209500), mutations in the hairless gene on chromosome 8p21 have recently been identified. Atrichia with papules also occurs in the clinical setting of vitamin D-dependent rickets type IIA (VDDR IIA; OMIM 277440), resulting from mutations in the vitamin D receptor gene on chromosome 12q12-q14. Despite the distinct genetic basis for both forms of atrichia, the clinical findings are strikingly similar and exhibit classic pathognomonic features unique to this phenotype. We sought to document the clinical and molecular features of APL and VDDR IIA. OBSERVATIONS Molecular analysis of the hairless and vitamin D receptor genes was performed on genomic DNA from probands and family members from 3 families with APL and 2 with VDDR IIA. We present a clinical and histologic comparison of atrichia in patients with APL and VDDR IIA and highlight the genetically heterogeneous basis of atrichia by identification of pathogenetic mutations. CONCLUSIONS Increased awareness of these diseases will allow early diagnosis and potential therapeutic intervention for the rickets in VDDR IIA and avoidance of treatment of the atrichia in both APL and VDDR IIA. Their phenotype similarities suggest the possibility of a functional relationship between HR and VDR.