Molecular genetic analysis of Rubinstein-Taybi syndrome in Russian patients

被引：0
作者：
Ismagilova, Olga R. [1 ]
Adyan, Tagui A. [1 ,2 ]
Beskorovainaya, Tatiana S. [1 ]
Polyakov, Alexander V. [1 ]
机构：
[1] Fed State Budgetary Sci Inst, Res Ctr Med Genet RCMG, DNA Diagnost Lab, Moscow, Russia
[2] Pirogov Russian Natl Res Med Univ, Fac Biomed Sci, Dept Gen & Med Genet, Moscow, Russia
来源：
FRONTIERS IN GENETICS | 2025年 / 16卷
关键词：
multiple congenital anomaly syndrome; Rubinstein-Taybi syndrome; CREBBP; EP300; next-generation sequencing; multiplex ligation-dependent probe amplification; MUTATIONS; CREBBP; CBP;
D O I：
10.3389/fgene.2025.1516565
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Introduction Rubinstein-Taybi syndrome (RSTS) is one of the many forms of syndromic intellectual disability, occurring in the population with a frequency of 1: 100-125 thousand newborns. The specific phenotype of patients enables the so-called "portrait" diagnosis of classical cases of RSTS, followed by the analysis of the CREBBP and EP300 genes, whose association with RSTS has been confirmed. Nevertheless, for approximately half of the patients in various cohorts, the diagnosis cannot be confirmed.Methods In this paper we present the results of a study of 158 Russian patients referred for molecular diagnosis of RSTS using multiplex ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS).Results Pathogenic and likely pathogenic variants were identified in 67 patients (42.4%), of which 62 (39%) were in CREBBP and 4 cases (2%)-in EP300. In one case, a known pathogenic variant in SRCAP, associated with Floating-Harbor syndrome (FHS), which is phenotypically similar to RSTS, was also identified; therefore, the possibilities and prospects for differential diagnosis were considered.
引用
收藏
页数：9
相关论文
共 25 条
  • [1] Banka S., Sayer R., Breen C., Barton S., Pavaine J., Sheppard S.E., Et al., Genotype–phenotype specificity in menke–hennekam syndrome caused by missense variants in exon 30 or 31 of CREBBP, Am. J. Med. Genet. A, 179, pp. 1058-1062, (2019)
  • [2] Bartsch O., Schmidt S., Richter M., Morlot S., Seemanova E., Wiebe G., Et al., DNA sequencing of CREBBP demonstrates mutations in 56% of patients with rubinstein–taybi syndrome (RSTS) and in another patient with incomplete RSTS, Hum. Genet, 117, pp. 485-493, (2005)
  • [3] Bentivegna A., Milani D., Gervasini C., Castronovo P., Mottadelli F., Manzini S., Et al., Rubinstein-taybi syndrome: spectrum of CREBBP mutations in Italian patients, BMC Med. Genet, 7, (2006)
  • [4] Bjornsson H.T., The mendelian disorders of the epigenetic machinery, Genome Res, 25, pp. 1473-1481, (2015)
  • [5] Cohen J.L., Schrier Vergano S.A., Mazzola S., Strong A., Keena B., McDougall C., Et al., EP300‐related rubinstein–taybi syndrome: highlighted rare phenotypic findings and a genotype–phenotype meta‐analysis of 74 patients, Am. J. Med. Genet. A, 182, pp. 2926-2938, (2020)
  • [6] Coupry I., Roudaut C., Stef M., Delrue M.-A., Marche M., Burgelin I., Et al., Molecular analysis of the CBP gene in 60 patients with rubinstein-taybi syndrome, J. Med. Genet, 39, pp. 415-421, (2002)
  • [7] Cross E., Duncan-Flavell P.J., Howarth R.J., Crooks R.O., Thomas N.S., Bunyan D.J., Screening of a large rubinstein–taybi cohort identified many novel variants and emphasizes the importance of the CREBBP histone acetyltransferase domain, Am. J. Med. Genet. A, 182, pp. 2508-2520, (2020)
  • [8] Cucco F., Sarogni P., Rossato S., Alpa M., Patimo A., Latorre A., Et al., Pathogenic Variants in EP300 and ANKRD11 in Patients with Phenotypes Overlapping Cornelia de Lange Syndrome, Am. J. Med. Genet. A, 182, pp. 1690-1696, (2020)
  • [9] Di Fede E., Massa V., Augello B., Squeo G., Scarano E., Perri A.M., Et al., Expanding the phenotype associated to KMT2A variants: overlapping clinical signs between wiedemann–steiner and rubinstein–taybi syndromes, Eur. J. Hum. Genet, 29, pp. 88-98, (2020)
  • [10] Enomoto Y., Yokoi T., Tsurusaki Y., Murakami H., Tominaga M., Minatogawa M., Et al., Divergent variant patterns among 19 patients with rubinstein‐taybi syndrome uncovered by comprehensive genetic analysis including whole genome sequencing, Clin. Genet, 101, 3, pp. 335-345, (2022)
123