Johnston Jennifer J, Olivos-Glander Isabelle, Turner Joyce, Aleck Kyrieckos, Bird Lynne M, Mehta Lakshmi, Schimke R Neil, Heilstedt Heidi, Spence J Edward, Blancato Jan, Biesecker Leslie G
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Am J Med Genet A. 2003 Dec 15;123A(3):236-42. doi: 10.1002/ajmg.a.20318.
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 conclude 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.
Greig头多指（趾）综合征（GCPS）由7号染色体短臂13区（7p13）的GLI3基因单倍剂量不足引起。GCPS的特征包括多指（趾）、巨头畸形和眼距过宽，并且可能与认知缺陷和胼胝体异常有关。GCPS患者的GLI3突变包括点突变、移码突变、易位和大片段缺失突变。对34例具有GCPS特征的患者进行了荧光原位杂交（FISH）和短串联重复序列多态性（STRP）分析。在11例患者中鉴定出缺失，并确定了其缺失范围。9例有缺失的患者存在智力发育迟缓（MR）或发育延迟（DD），被归类为重度GCPS。这些重度GCPS患者具有与胼胝体发育不全综合征（ACLS）重叠的表现。对6例缺失大小在151 kb至10.6 Mb之间的患者的缺失断点进行了分析。发现连接片段各不相同，断点两侧没有共同序列。我们得出结论，由包括GLI3在内的大片段缺失引起的GCPS患者可能存在认知缺陷，并且我们推测这种重度GCPS表型是由相邻基因的缺失所致。
