Effect of the size of the deletion and clinical manifestation in Wolf-Hirschhorn syndrome:: analysis of 13 patients with a de novo deletion
Effect of the size of the deletion and clinical manifestation in Wolf-Hirschhorn syndrome:: analysis of 13 patients with a de novo deletion
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DOI：
10.1038/sj.ejhg.5200498
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发表时间：
2000-07-01
影响因子：
5.2
通讯作者：
Gillessen-Kaesbach, G
中科院分区：
文献类型：
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作者：
Wieczorek, D;Krause, M;Gillessen-Kaesbach, G
我们对 13 名由于 4p 染色体从头缺失而患有 Wolf-Hirschhorn 综合征的患者（8 名女性和 5 名男性，年龄 6 个月至 13 岁）进行了临床、细胞遗传学和分子分析。所有患者均表现出典型的面部完形、小头畸形和严重智力低下。其他临床症状包括低出生体重（10/13；77%）、产后身材矮小（8/12；66%）、肌张力低下（12/13；92%）、癫痫发作（11/13；85%）、先天性心脏缺陷（4/13；31%）、虹膜缺损（4/12；33%）、生殖器异常（4/13；31%）、耳聋（3/13；23%）和肾脏异常（3/13；23%）。最小的缺失是近 2.5 Mb 的亚显微末端缺失。最大的是近 30 Mb 的末端删除。唇裂/腭裂、耳前凹陷/耳垂和先天性心脏缺陷仅出现在末端缺失大于 10Mb 的患者中。平均出生体重、出生身长和出生后头围的偏差与缺失的大小相关。用微卫星标记确定缺失的亲本起源，三名患者中母体等位基因缺失，八名患者中父系等位基因缺失。我们的观察结果支持沃尔夫-赫希霍恩综合征中存在部分基因型-表型相关性。
We performed clinical, cytogenetic, and molecular analyses on 13 patients (8 females and 5 males, aged 6 months to 13 years) with Wolf-Hirschhorn syndrome due to de novo deletions of chromosome 4p. All patients presented with the typical facial gestalt, microcephaly, and profound mental retardation. Other clinical signs were low birth weight (10/13; 77%), postnatal short stature (8/12; 66%), muscular hypotonia (12/13; 92%), seizures (11/13; 85%), congenital heart defects (4/13; 31%), colobomata of iris (4/12; 33%), genital anomalies (4/13; 31%), deafness (3/13; 23%), and renal anomalies (3/13; 23%). The smallest deletion was a submicroscopic terminal deletion of nearly 2.5 Mb. The largest was a terminal deletion of nearly 30 Mb. Cleft lip/palate, preauricular pits/tags, and congenital heart defects were present only in patients with terminal deletions larger than 10Mb. The deviations from mean birth weight, birth length, and postnatal head circumference correlated with the size of the deletion. Determining the parental origin of the deletion with microsatellite markers, the maternal allele was missing in three patients and the paternal allele in eight patients. Our observations support the existence of a partial genotype-phenotype correlation in Wolf-Hirschhorn syndrome.