Primrose syndrome: a phenotypic comparison of patients with a ZBTB20 missense variant versus a 3q13.31 microdeletion including ZBTB20

被引:7
|
作者
Juven, Aurelien [1 ,2 ]
Nambot, Sophie [1 ,2 ,3 ,4 ,5 ,6 ]
Piton, Amelie [7 ]
Jean-Marcais, Nolwenn [1 ,2 ,4 ,5 ]
Masurel, Alice [1 ,2 ,4 ,5 ]
Callier, Patrick [3 ,4 ,5 ,6 ]
Marle, Nathalie [3 ]
Mosca-Boidron, Anne-Laure [3 ,6 ]
Kuentz, Paul [3 ,6 ]
Philippe, Christophe [3 ,6 ]
Chevarin, Martin [3 ,6 ]
Duffourd, Yannis [3 ,6 ]
Gautier, Elodie [1 ,2 ]
Munnich, Arnold [8 ,9 ]
Rio, Marlene [8 ,9 ]
Rondeau, Sophie [10 ]
El Chehadeh, Salima [11 ]
Schaefer, Elise [11 ]
Gerard, Benedicte [7 ]
Bouquillon, Sonia [12 ]
Delorme, Catherine Vincent [13 ]
Francannet, Christine [14 ]
Laffargue, Fanny [14 ]
Gouas, Laetitia [15 ]
Isidor, Bertrand [16 ]
Vincent, Marie [16 ]
Blesson, Sophie [17 ]
Giuliano, Fabienne [18 ]
Pichon, Olivier [19 ]
Le Caignec, Cedric [19 ]
Journel, Hubert [20 ]
Perrin-Sabourin, Laurence [21 ]
Fabre-Teste, Jennifer [21 ]
Martin, Dominique [22 ]
Vieville, Gaelle [23 ]
Dieterich, Klaus [24 ]
Lacombe, Didier [25 ]
Denomme-Pichon, Anne-Sophie [1 ,2 ,3 ,4 ,5 ,6 ]
Thauvin-Robinet, Christel [1 ,2 ,3 ,4 ,5 ,6 ]
Faivre, Laurence [1 ,2 ,4 ,5 ,6 ]
机构
[1] CHU Dijon, Hop Enfants, Ctr Genet, Dijon, France
[2] CHU Dijon, Hop Enfants, Ctr Reference Anomalies Dev & Syndromes Malformat, Dijon, France
[3] CHU Dijon, Lab Genet Mol, UF Innovat Diagnost Genom Malad Rares, Plateau Tech Biol, Dijon, France
[4] CHU Dijon, Federat Hosp Univ Med Translat & Anomalies Dev FH, Dijon, France
[5] Univ Bourgogne Franche Comte, Dijon, France
[6] Univ Bourgogne Franche Comte, Genet Anomalies Developpement, Inserm 1231, UMR,GAD Team, F-21000 Dijon, France
[7] CHU Strasbourg, Unite Biol & Genet Mol, Strasbourg, France
[8] Inst Imagine, Paris, France
[9] Hop Necker Enfants, Inserm U781, Paris, France
[10] Hop Necker Enfants Malad, Serv Genet Mol, Paris, France
[11] CHU Strasbourg, Serv Genet Med, Strasbourg, France
[12] Ctr Hosp Reg Univ Lille, Hop Jeanne de Flandre, Inst Genet Med, Lille, France
[13] Ctr Hosp Reg Univ Lille, Hop Jeanne de Flandre, Pole Biol Pathol Genet, Lille, France
[14] Ctr Hosp Univ Estaing, Serv Genet Med, Clermont Ferrand, France
[15] Ctr Hosp Univ, Serv Cytogenet Med, Clermont Ferrand, France
[16] CHU Nantes, Serv Genet Med, Nantes, France
[17] CHU Tours, Hop Bretonneau Tours, Serv Genet, Tours, France
[18] CHU Nice, Serv Genet Med, Nice, France
[19] CHU Nantes, Unite Genet Chromosom Cytogenet, Nantes, France
[20] Ctr Hosp Bretagne Atlantique, Serv Genet Med, Vannes, France
[21] Hop Robert Debre, Dept Genet, Paris, France
[22] Ctr Hosp Le Mans, Lab Genet Med & Cytogenet, Le Mans, France
[23] CHU Grenoble, Serv Genet Chromosom, Grenoble, France
[24] CHU Grenoble, Site Nord, Pole Couple Enfant, Unite Genet Clin, Grenoble, France
[25] CHU Bordeaux, Serv Genet Med, GH Pellegrin, Bordeaux, France
关键词
INTELLECTUAL DISABILITY; DEVELOPMENTAL DELAY; MUTATIONS; DIAGNOSIS;
D O I
10.1038/s41431-020-0582-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Primrose syndrome is characterized by variable intellectual deficiency, behavior disorders, facial features with macrocephaly, and a progressive phenotype with hearing loss and ectopic calcifications, distal muscle wasting, and contractures. In 2014, ZBTB20 variants were identified as responsible for this syndrome. Indeed, ZBTB20 plays an important role in cognition, memory, learning processes, and has a transcription repressive effect on numerous genes. A more severe phenotype was discussed in patients with missense single nucleotide variants than in those with large deletions. Here, we report on the clinical and molecular results of 14 patients: 6 carrying ZBTB20 missense SNVs, 1 carrying an early truncating indel, and 7 carrying 3q13.31 deletions, recruited through the AnDDI-Rares network. We compared their phenotypes and reviewed the data of the literature, in order to establish more powerful phenotype-genotype correlations. All 57 patients presented mild-to-severe ID and/or a psychomotor delay. Facial features were similar with macrocephaly, prominent forehead, downslanting palpebral fissures, ptosis, and large ears. Hearing loss was far more frequent in patients with missense SNVs (p = 0.002), ectopic calcification, progressive muscular wasting, and contractures were observed only in patients with missense SNVs (p nonsignificant). Corpus callosum dysgenesis (p = 0.00004), hypothyroidism (p = 0.047), and diabetes were also more frequent in this group. However, the median age was 9.4 years in patients with deletions and truncating variant compared with 15.1 years in those with missense SNVs. Longer follow-up will be necessary to determine whether the phenotype of patients with deletions is also progressive.
引用
收藏
页码:1044 / 1055
页数:12
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