Genotype-phenotype correlations in patients with retinoblastoma and interstitial 13q deletions
Genotype-phenotype correlations in patients with retinoblastoma and interstitial 13q deletions
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DOI：
10.1038/ejhg.2011.58
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发表时间：
2011-09-01
影响因子：
5.2
通讯作者：
Lohmann, Dietmar
中科院分区：
文献类型：
--
作者：
Mitter, Diana;Ullmann, Reinhard;Lohmann, Dietmar
含有RB 1基因的间质性13 q缺失的患者显示视网膜母细胞瘤和可变的临床特征。表型表达与特定邻近基因丢失之间的关系尚未解决。我们获得了63例间质性13 q缺失涉及RB 1的患者的临床，细胞遗传学和分子数据。对38例患者进行了全基因组阵列分析或定制的13q14.11q14.3高分辨率阵列分析，对54例患者进行了细胞遗传学分析。缺失的大小范围在4.2 kb和超过33.43 Mb之间;断点是非复发性的。5例患者缺失连接的序列分析显示微同源性和2-34个碱基对的插入提示非同源末端连接。视网膜母细胞瘤的轻度表型表达在缺失大于1 Mb的患者中观察到，其中包含MED 4基因。比较小（13 q14内），中（13q12.3q21.2内）和大（13q12q31.2内）缺失患者的临床特征。具有小缺失的患者可表现为大头畸形、高身材、肥胖、运动和/或言语延迟。中度缺失的患者表现出特征性的面部特征，轻度至中度的精神发育迟滞，身材矮小和小头畸形。大缺失的患者具有特征性颅面畸形、身材矮小、小头畸形、轻度至重度精神发育迟缓、肌张力减退、便秘和进食问题。其他特征包括耳聋、癫痫发作、大脑和心脏异常。我们没有发现临床特征和父母来源的缺失之间的相关性。我们的数据表明，NUFIP 1和PCDH 8的半合子的损失可能有助于精神发育迟缓，MTLR 1的缺失导致小头畸形，EDNRB的损失导致进食困难和耳聋。European Journal of Human Genetics（2011）19，947-958; doi：10.1038/ejhg.2011.58; 2011年4月20日在线发表
Patients with an interstitial 13q deletion that contains the RB1 gene show retinoblastoma and variable clinical features. Relationship between phenotypic expression and loss of specific neighboring genes are unresolved, yet. We obtained clinical, cytogenetic and molecular data in 63 patients with an interstitial 13q deletion involving RB1. Whole-genome array analysis or customized high-resolution array analysis for 13q14.11q14.3 was performed in 38 patients, and cytogenetic analysis was performed in 54 patients. Deletion sizes ranged between 4.2 kb and more than 33.43 Mb; breakpoints were non-recurrent. Sequence analysis of deletion junctions in five patients revealed microhomology and insertion of 2-34 base pairs suggestive of non-homologous end joining. Milder phenotypic expression of retinoblastoma was observed in patients with deletions larger than 1 Mb, which contained the MED4 gene. Clinical features were compared between patients with small (within 13q14), medium (within 13q12.3q21.2) and large (within 13q12q31.2) deletions. Patients with a small deletion can show macrocephaly, tall stature, obesity, motor and/or speech delay. Patients with a medium deletion show characteristic facial features, mild to moderate psychomotor delay, short stature and microcephaly. Patients with a large deletion have characteristic craniofacial dysmorphism, short stature, microcephaly, mild to severe psychomotor delay, hypotonia, constipation and feeding problems. Additional features included deafness, seizures and brain and heart anomalies. We found no correlation between clinical features and parental origin of the deletion. Our data suggest that hemizygous loss of NUFIP1 and PCDH8 may contribute to psychomotor delay, deletion of MTLR1 to microcephaly and loss of EDNRB to feeding difficulties and deafness. European Journal of Human Genetics (2011) 19, 947-958; doi: 10.1038/ejhg.2011.58; published online 20 April 2011