Menke-Hennekam综合征表型及基因型分析
收稿日期: 2022-11-29
网络出版日期: 2023-08-10
基金资助
国家自然科学基金面上项目(81873724);上海市自然科学基金项目(20ZR1472700)
Clinical characteristics and genetic analysis in Chinese patients with Menke-Hennekam syndrome
Received date: 2022-11-29
Online published: 2023-08-10
目的 探讨CREBBP基因变异所致Menke-Hennekam综合征（MKHK）的临床特征及基因变异特点。方法 回顾性总结7例中国MKHK患儿临床特征及基因测序结果。结果 7例患儿均有精神发育迟缓、语言及运动发育落后、身材矮小，特殊面容表现为上斜眼睑、内眦距宽、塌鼻梁、短鼻、长人中、招风耳、低耳位、小下颌，2例伴喂养问题，4例伴视力障碍，3例伴听力障碍，3例伴脑发育异常，2例合并手/脚部异常体征。7例患儿携带CREBBP基因的致病/可能致病变异，均位于外显子30和31，共6个不同变异，涉及2种类型基因变异（5个为错义变异、1个为不影响阅读框的插入缺失），全为新发，其中c.5218C>T、c.5225T>A（NM_004380.3）变异尚未有文献报道。结论 MKHK是一种罕见的常染色体显性遗传病，大多由CREBBP基因第30或31位外显子杂合错义变异引起。文章报道了CREBBP基因的6个变异，进一步扩大了MKHK的基因变异谱。
关键词： Menke-Hennekam 综合征; Rubinstein-Taybi综合征; 智力障碍; 发育迟缓; CREBBP基因; 基因变异
唐雅楠 , 叶贤涛 , 顾学范 , 余永国 , 肖冰 , 孙昱 . Menke-Hennekam综合征表型及基因型分析[J]. 临床儿科杂志, 2023 , 41(8) : 613 -617 . DOI: 10.12372/jcp.2023.22e1597
ObjectiveTo explore the clinical phenotype and identify genetic variations in Chinese patients with Menke-Hennekam syndrome (MKHK). Methods The clinical and genetic data of seven children with MKHK were retrospectively analyzed. Results All of the seven children are presented with psychomotor developmental delay, variable degree of intellectual disability, short stature, and facial dysmorphism (including short and upslanted palpebral fissures, telecanthi, depressed nasal bridge, short nose, long philtrum, protruding or low-set ears and micrognathia), accompanied by other manifestations (2/7 feeding problems, 4/7 visual impairment, 3/7 hearing impairment, 3/7 cerebral anomaly, 2/7 distal limb malformation). The genetic findings of patientsinvolve six different variants: five missense and one in-frame deletion), all of which arose de novo. c.5218C>T and c.5225T>A (NM_004380.3) variants have not been reported previously in literature. Conclusion MKHK is a rare autosomal dominant genetic disease, most of which are caused by heterozygous missense variation in the end of exon 30 and the beginning of exon 31 of CREBBP. This study revealed six de novo variants of CREBBP, further expanding the genetic spectrum of MKHK.
| [1] | Menke LA, van Belzen MJ, Alders M, et al. CREBBP mutations in individuals without Rubinstein-Taybi syndrome phenotype[J]. Am J Med Genet A, 2016, 170(10): 2681-2693. |
| [2] | Menke LA, DDD study, Gardeitchik T, et al. Further delineation of an entity caused by CREBBP and EP300 mutations but not resembling Rubinstein-Taybi syndrome[J]. Am J Med Genet A, 2018, 176(4): 862-876. |
| [3] | Angius A, Uva P, Oppo M, et al. Confirmation of a new phenotype in an individual with a variant in the last part of exon 30 of CREBBP[J]. Am J Med Genet A, 2019, 179(4): 634-638. |
| [4] | Banka S, Sayer R, Breen C, et al. Genotype-phenotype specificity in Menke-Hennekam syndrome caused by missense variants in exon 30 or 31 of CREBBP[J]. Am J Med Genet A, 2019, 179(6): 1058-1062. |
| [5] | Nishi E, Takenouchi T, Miya F, et al. The novel and recurrent variants in exon 31 of CREBBP in Japanese patients with Menke-Hennekam syndrome[J]. Am J Med Genet A, 2022, 188(2): 446-453. |
| [6] | Sima A, Sm?deanu RE, Simionescu AA, et al. Menke-Hennekam syndrome: a literature review and a new case report[J]. Children (Basel), 2022, 9(5): 759. |
| [7] | Hennekam RC. Rubinstein-Taybi syndrome[J]. Eur J Hum Genet, 2006, 14(9): 981-985. |
| [8] | Stevens CA. Rubinstein-Taybi syndrome[M]// Adam MP, Everman DB, Mirzaa GM, et al. GeneReviews? [Internet]. Seattle (WA): University of Washington, 1993-2022. |
| [9] | Allanson JE, Cunniff C, Hoyme HE, et al. Elements of morphology: standard terminology for the head and face[J]. Am J Med Genet A, 2009, 149A(1): 6-28. |
| [10] | Carey JC, Cohen MM Jr, Curry CJ, et al. Elements of morphology: standard terminology for the lips, mouth, and oral region[J]. Am J Med Genet A, 2009, 149A(1): 77-92. |
| [11] | Hall BD, Graham JM Jr, Cassidy SB, et al. Elements of morphology: standard terminology for the periorbital region[J]. Am J Med Genet A, 2009, 149A(1): 29-39. |
| [12] | Hennekam RC, Cormier-Daire V, Hall JG, et al. Elements of morphology: standard terminology for the nose and philtrum[J]. Am J Med Genet A, 2009, 149A(1): 61-76. |
| [13] | Hunter A, Frias JL, Gillessen-Kaesbach G, et al. Elements of morphology: standard terminology for the ear[J]. Am J Med Genet A, 2009, 149A(1): 40-60. |
| [14] | Biesecker LG, Adam MP, Chung BH, et al. Elements of morphology: standard terminology for the trunk and limbs[J]. Am J Med Genet A, 2022, 188(11): 3191-3228. |
| [15] | de La Dure-Molla M, Fournier BP, Manzanares MC, et al. Elements of morphology: standard terminology for the teeth and classifying genetic dental disorders[J]. Am J Med Genet A, 2019, 179(10): 1913-1981. |
| [16] | Biesecker LG, Aase JM, Clericuzio C, et al. Elements of morphology: standard terminology for the hands and feet[J]. Am J Med Genet A, 2009, 149A(1): 93-127. |
| [17] | Hennekam RC, Biesecker LG, Allanson JE, et al. Elements of morphology: general terms for congenital anomalies[J]. Am J Med Genet A, 2013, 161A(11): 2726-2733. |
| [18] | Hennekam RC, Allanson JE, Biesecker LG, et al. Elements of morphology: standard terminology for the external genitalia[J]. Am J Med Genet A, 2013, 161A(6): 1238-1263. |
| [19] | Van Gils J, Magdinier F, Fergelot P, et al. Rubinstein-Taybi syndrome: a model of epigenetic disorder[J]. Genes (Basel), 2021, 12(7): 968. |
| [20] | Lipinski M, Del Blanco B, Barco A. CBP/p300 in brain development and plasticity: disentangling the KAT's cradle[J]. Curr Opin Neurobiol, 2019, 59: 1-8. |
| [21] | Lipinski M, Mu?oz-Viana R, Del Blanco B, et al. KAT3-dependent acetylation of cell type-specific genes maintains neuronal identity in the adult mouse brain[J]. Nat Commun, 2020, 11(1): 2588. |
| [22] | Larizza L, Calzari L, Alari V, et al. Genes for RNA-binding proteins involved in neural-specific functions and diseases are downregulated in Rubinstein-Taybi iNeurons[J]. Neural Regen Res, 2022, 17(1): 5-14. |
/
| 〈 |
|
〉 |
沪公网安备 31011002000392号
