Indexado en

Licencia y uso

Citaciones

Cited 2 times in

Cited 1 times in

Cited 3 times in

Cited 3 times in

Altmetrics

Grant support

This work was supported in part by Telethon Undiagnosed Diseases Program (TUDP,GSP15001), ISCIII-Feder funds: grants FIS PI20/01053, PMP22/00049.

Análisis de autorías institucional

Compartir

Snijders Blok-Campeau Syndrome: Description of 20 Additional Individuals with Variants in CHD3 and Literature Review

Publicado en:Genes. 14 (9): 1664- - 2023-09-01 14(9), DOI: 10.3390/genes14091664

Autores: Pascual, Patricia; Tenorio-Castano, Jair; Mignot, Cyril; Afenjar, Alexandra; Arias, Pedro; Gallego-Zazo, Natalia; Parra, Alejandro; Miranda, Lucia; Cazalla, Mario; Silvan, Cristina; Heron, Delphine; Keren, Boris; Popa, Ioana; Palomares, Maria; Rikeros, Emi; Ramos, Feliciano J; Almoguera, Berta; Ayuso, Carmen; Swafiri, Saoud Tahsin; Barbero, Ana Isabel Sanchez; Srinivasan, Varunvenkat M; Gowda, Vykuntaraju K; Morleo, Manuela; Nigro, Vicenzo; D'Arrigo, Stefano; Ciaccio, Claudia; Mesa, Carmen Martin; Paumard, Beatriz; Guillen, Gema; Anton, Ana Teresa Serrano; Jimenez, Marta Dominguez; Seidel, Veronica; Suarez, Julia; Cormier-Daire, Valerie; Nevado, Julian; Lapunzina, Pablo

Afiliaciones

Resumen

Snijders Blok-Campeau syndrome (SNIBCPS, OMIM# 618205) is an extremely infrequent disease with only approximately 60 cases reported so far. SNIBCPS belongs to the group of neurodevelopmental disorders (NDDs). Clinical features of patients with SNIBCPS include global developmental delay, intellectual disability, speech and language difficulties and behavioral disorders like autism spectrum disorder. In addition, patients with SNIBCPS exhibit typical dysmorphic features including macrocephaly, hypertelorism, sparse eyebrows, broad forehead, prominent nose and pointed chin. The severity of the neurological effects as well as the presence of other features is variable among subjects. SNIBCPS is caused likely by pathogenic and pathogenic variants in CHD3 (Chromodomain Helicase DNA Binding Protein 3), which seems to be involved in chromatin remodeling by deacetylating histones. Here, we report 20 additional patients with clinical features compatible with SNIBCPS from 17 unrelated families with confirmed likely pathogenic/pathogenic variants in CHD3. Patients were analyzed by whole exome sequencing and segregation studies were performed by Sanger sequencing. Patients in this study showed different pathogenic variants affecting several functional domains of the protein. Additionally, none of the variants described here were reported in control population databases, and most computational predictors suggest that they are deleterious. The most common clinical features of the whole cohort of patients are global developmental delay (98%) and speech disorder/delay (92%). Other frequent features (51-74%) include intellectual disability, hypotonia, hypertelorism, abnormality of vision, macrocephaly and prominent forehead, among others. This study expands the number of individuals with confirmed SNIBCPS due to pathogenic or likely pathogenic variants in CHD3. Furthermore, we add evidence of the importance of the application of massive parallel sequencing for NDD patients for whom the clinical diagnosis might be challenging and where deep phenotyping is extremely useful to accurately manage and follow up the patients.

Palabras clave