1例Rubinstein-Taybi综合征的临床及CREBBP基因新突变分析
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摘要
患儿女,3岁8个月,出生身长、体重正常。生后喂养困难。身高、体重及头围均低于第3百分位,伴智力障碍,面容特别,表现为拱形粗眉、眼裂下斜、宽鼻梁,但无喙状鼻尖、宽大的拇指及脚趾,基本符合Rubinstein-Taybi综合征(RSTS)的临床表现。基因测序发现患儿CREBBP基因c.3779+1G>T杂合剪接位点突变,其父母该位点无变异,患儿明确诊断为RSTS。c.3779+1G>T在人类基因突变数据库中未见报道,为新的致病性突变。确诊后主要针对患儿语言及运动发育落后进行康复训练。目前患儿门诊随访3个月,尚未评估康复治疗疗效。
The patient was a girl aged 3 years and 8 months with normal body length and body weight at birth.The girl had feeding difficulty after birth.Her height,body weight,and head circumference were below the 3 rd percentile.She had intellectual disability and an unusual facies manifesting as arched shaggy eyebrows,down-slanting palpebral fissures,and broad nasal bridge,but had no a beaked nose,broad thumbs,or big toes.These clinical manifestations were basically consistent with Rubinstein-Taybi syndrome(RSTS).Gene sequencing identified a heterozygous splice site mutation,c.3779 T+1 G>T,in the CREBBP gene,which did not exist in her parents.Therefore,a definite diagnosis of RSTS was made.The mutation c.3779 T+1 G>T had not been reported in the Human Gene Mutation Database and was identified as a novel pathogenic mutation.Then the girl was given rehabilitation training for delayed language and motor development.The girl has been followed up for 3 months in the outpatient department,but the effect of rehabilitation treatment has not been evaluated.
The patient was a girl aged 3 years and 8 months with normal body length and body weight at birth.The girl had feeding difficulty after birth.Her height,body weight,and head circumference were below the 3 rd percentile.She had intellectual disability and an unusual facies manifesting as arched shaggy eyebrows,down-slanting palpebral fissures,and broad nasal bridge,but had no a beaked nose,broad thumbs,or big toes.These clinical manifestations were basically consistent with Rubinstein-Taybi syndrome(RSTS).Gene sequencing identified a heterozygous splice site mutation,c.3779 T+1 G>T,in the CREBBP gene,which did not exist in her parents.Therefore,a definite diagnosis of RSTS was made.The mutation c.3779 T+1 G>T had not been reported in the Human Gene Mutation Database and was identified as a novel pathogenic mutation.Then the girl was given rehabilitation training for delayed language and motor development.The girl has been followed up for 3 months in the outpatient department,but the effect of rehabilitation treatment has not been evaluated.
引文
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[5]王艳,洪小杨,彭薇,等.应用单核苷酸多态性微阵列技术诊断Rubinstein-Taybi综合征1例报告[J].临床儿科杂志,2016,34(9):686-688.
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[11]Burke SL,Maramaldi P.The Social Security Administration's Compassionate Allowances Initiative:condition spotlight on Rubinstein-Taybi syndrome[J].Health Soc Work,2017,42(1):e32-e43.
[12]Wiley S.Rubinstein-Taybi syndrome medical guidelines[J].Am J Med Genet A,2003,119A(2):101-110.
[13]Waite J,Moss J,Beck SR,et al.Repetitive behavior in Rubinstein-Taybi syndrome:parallels with autism spectrum phenomenology[J].J Autism Dev Disord,2015,45(5):1238-1253.
[14]Wincent J,Luthman A,van Belzen M,et al.CREBBP and EP300 mutational spectrum and clinical presentations in a cohort of Swedish patients with Rubinstein-Taybi syndrome[J].Mol Genet Genomic Med,2015,4(1):39-45.
[15]Bartsch O,Locher K,Meinecke P,et al.Molecular studies in 10cases of Rubinstein-Taybi syndrome,including a mild variant showing a missense mutation in codon 1175 of CREBBP[J].J Med Genet,2002,39(7):496-501.
[16]Schorry EK,Keddache M,Lanphear N,et al.Genotypephenotype correlations in Rubinstein-Taybi syndrome[J].Am J Med Genet A,2008,146A(19):2512-2519.
[17]Murata T,Kurokawa R,Krones A,et al.Defect of histone acetyl transferase activity of the nuclear transcriptional coactivator CBP in Rubinstein-Taybi syndrome[J].Hum Mol Genet,2001,10(10):1071-1076.
[18]Bartsh O,Rasi S,Delicado A,et al.Evidence for a new contiguous gene syndrome,the chromosoma 16p13.3 deletion syndrome alias severe Rubinstein-Taybi syndrome[J].Hum Genet,2006,120(2):179-186.
[2]Milani D,Manzoni FM,Pezzani L,et al.Rubinstein-Taybi syndrome:clinical features,genetic basis,diagnosis,and management[J].Ital J Pediatr,2015,41:4.
[3]Roelfsema JH,Peters DJ.Rubinstein-Taybi syndrome:clinical and molecular overview[J].Expert Rev Mol Med,2007,9(23):1-16.
[4]张江伟,王长燕,李明,等.CREBBP基因突变所致Rubinstein-Taybi综合征二例临床和遗传学特征[J].中华儿科杂志,2014,52(9):673-677.
[5]王艳,洪小杨,彭薇,等.应用单核苷酸多态性微阵列技术诊断Rubinstein-Taybi综合征1例报告[J].临床儿科杂志,2016,34(9):686-688.
[6]廖若西,姜艳,王鸥,等.CREBBP基因突变导致的伴有双侧股骨头坏死的Rubinstein-Taybi综合征1例[J].中华骨质疏松和骨矿盐疾病杂志,2015,8(4):343-346.
[7]Spena S,Milani D,Rusconi D,et al.Insights into genotypephenotype correlations from CREBBP point mutation screening in a cohort of 46 Rubinstein-Taybi syndrome patients[J].Clin Genet,2015,88(5):431-440.
[8]Hutchinson DT,Sullivan R.Rubinstein-Taybi syndrome[J].J Hand Surg Am,2015,40(8):1711-1712.
[9]Hosek J,BorkováA.The Rubinstein-Taybi syndrome or a broad thumb-hallux syndrome[J].Cas Lek Cesk,2008,147(3):136-140.
[10]Sharma N,Mali AM,Bapat SA.Spectrum of CREBBP mutations in Indian patients with Rubinstein-Taybi syndrome[J].J Biosci,2010,35(2):187-202.
[11]Burke SL,Maramaldi P.The Social Security Administration's Compassionate Allowances Initiative:condition spotlight on Rubinstein-Taybi syndrome[J].Health Soc Work,2017,42(1):e32-e43.
[12]Wiley S.Rubinstein-Taybi syndrome medical guidelines[J].Am J Med Genet A,2003,119A(2):101-110.
[13]Waite J,Moss J,Beck SR,et al.Repetitive behavior in Rubinstein-Taybi syndrome:parallels with autism spectrum phenomenology[J].J Autism Dev Disord,2015,45(5):1238-1253.
[14]Wincent J,Luthman A,van Belzen M,et al.CREBBP and EP300 mutational spectrum and clinical presentations in a cohort of Swedish patients with Rubinstein-Taybi syndrome[J].Mol Genet Genomic Med,2015,4(1):39-45.
[15]Bartsch O,Locher K,Meinecke P,et al.Molecular studies in 10cases of Rubinstein-Taybi syndrome,including a mild variant showing a missense mutation in codon 1175 of CREBBP[J].J Med Genet,2002,39(7):496-501.
[16]Schorry EK,Keddache M,Lanphear N,et al.Genotypephenotype correlations in Rubinstein-Taybi syndrome[J].Am J Med Genet A,2008,146A(19):2512-2519.
[17]Murata T,Kurokawa R,Krones A,et al.Defect of histone acetyl transferase activity of the nuclear transcriptional coactivator CBP in Rubinstein-Taybi syndrome[J].Hum Mol Genet,2001,10(10):1071-1076.
[18]Bartsh O,Rasi S,Delicado A,et al.Evidence for a new contiguous gene syndrome,the chromosoma 16p13.3 deletion syndrome alias severe Rubinstein-Taybi syndrome[J].Hum Genet,2006,120(2):179-186.