Clinical and molecular delineation of the greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome
Clinical and molecular delineation of the greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome
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DOI：
10.1002/ajmg.a.20318
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发表时间：
2003-12-15
影响因子：
2
通讯作者：
Biesecker, LG
中科院分区：
文献类型：
--
作者：
Johnston, JJ;Olivos-Glander, I;Biesecker, LG
Greig头多并指综合征（GCPS）是由7 p13上GLI 3的单倍不足引起的。GCPS的特征包括多指（趾）畸形、大头畸形和距离过远，并且可能与认知缺陷和胼胝体异常有关。GCPS患者中的GLI 3突变包括点突变、移码突变、易位突变和总缺失突变。对34例具有GCPS特征的患者进行了FISH和STRP分析。在11例患者中发现缺失，并确定其缺失程度。9例缺失患者有智力低下（MR）或发育迟缓（DD），并被归类为严重GCPS。这些严重的GCPS患者的表现与acrocallosal综合征（ACLS）重叠。分析了6例患者的缺失断点，其缺失大小从151 kb到10.6 Mb不等。发现连接片段是不同的，断裂点侧翼没有共同的序列。我们得出结论，包括GLI 3在内的大缺失导致的GCPS患者可能有认知缺陷，我们假设这种严重的GCPS表型是由相邻基因缺失引起的。2003年出版Wiley-Liss，Inc.
Greig cephalopolysyndactyly syndrome (GCPS) is caused by haploinsufficiency of GLI3 on 7p13. Features of GCPS include polydactyly, macrocephaly, and hypertelorism, and may be associated with cognitive deficits and abnormalities of the corpus callosum. GLI3 mutations in GCPS patients include point, frameshift, translocation, and gross deletion mutations. FISH and STRP analyses were applied to 34 patients with characteristics of GCPS. Deletions were identified in 11 patients and the extent of their deletion was determined. Nine patients with deletions had mental retardation (MR) or developmental delay (DD) and were classified as severe GCPS. These severe GCPS patients have manifestations that overlap with the acrocallosal syndrome (ACLS). The deletion breakpoints were analyzed in six patients whose deletions ranged in size from 151 kb to 10.6 Mb. Junction fragments were found to be distinct with no common sequences flanking the breakpoints. We con-clude that patients with GCPS caused by large deletions that include GLI3 are likely to have cognitive deficits, and we hypothesize that this severe GCPS phenotype is caused by deletion of contiguous genes. Published 2003 Wiley-Liss, Inc.