Publicação
Multiple non-contiguous interstitial deletions in 5q21q22.1, including the CHD1 gene, identified in a boy with developmental delay and severe language impairment
| datacite.subject.fos | Ciências Médicas::Ciências da Saúde | |
| dc.contributor.author | Marques, Bárbara | |
| dc.contributor.author | Pedro, Sónia | |
| dc.contributor.author | Serafim, Sílvia | |
| dc.contributor.author | Tarelho, Ana Rita | |
| dc.contributor.author | Ferreira, Cristina | |
| dc.contributor.author | Catanho, Joana Adelaide | |
| dc.contributor.author | Moreira, Ana | |
| dc.contributor.author | Carvalho, Inês | |
| dc.contributor.author | Correia, Hildeberto | |
| dc.date.accessioned | 2026-03-04T13:10:24Z | |
| dc.date.available | 2026-03-04T13:10:24Z | |
| dc.date.issued | 2025-06-29 | |
| dc.description.abstract | Intellectual disability (ID), developmental delay (DD), and behavioural disorders are complex neurodevelopmental conditions associated with multifactorial etiologies, including genetic factors. Chromosomal microarray analysis (CMA) is a valuable tool in identifying copy number variations (CNVs) contributing to neurodevelopmental disorders. Here we report a 4-year-old male with DD, severe language impairment, behavioral disturbances, macrocephaly, facial dysmorphisms, and delay walking (at 20 months). He was born to nonconsanguineous parents. Family history is significant for maternal intellectual disability and paternal neonatal hypoxic-ischemic encephalopathy, which resulted in hemiparesis and language impairment. CMA revealed three heterozygous interstitial deletions: 2.12Mb at 5q15q21.1(97929163-100045362), encompassing the CHD1 gene; 684Kb at 5q21.3(104580978-105264711), a gene-free region; and 3.69Mb at 5q21.3q22.1(107047547-110727429), including the SLC25A46 gene. Parental segregation studies revealed that all three deletions were maternally inherited. Although the identified non-contiguous losses may suggest a complex chromosomal rearrangement (CCR), no further studies were performed. Interstitial deletions of the middle region of the long arm of chromosome 5 are rare, and cases of CCR involving only this chromosome are even more rare. Most of the CCR are associated to intellectual disability. Missense variants in CHD1 have been associated with Pilarowski-Bjornsson syndrome, a neurodevelopmental disorder characterized by ID, DD, dysmorphic features, and apraxia of speech. However, deletion involving this gene are rare and may lead to speech abnormalities in the absence of intellectual disability (ID) or other major neurodevelopmental disorders. This phenotypic variability suggests that both CHD1 deletions and missense variants may exhibit variable expressivity or incomplete penetrance. This case highlights a possible link between CHD1 deletion and an autosomal dominant complex neurodevelopmental disorder and the diagnostic utility of cytogenetic studies in identifying complex genetic etiologies underlying CCR. | eng |
| dc.identifier.uri | http://hdl.handle.net/10400.18/11120 | |
| dc.language.iso | eng | |
| dc.peerreviewed | yes | |
| dc.rights.uri | N/A | |
| dc.subject | Chromosomal Microarray Analysis | |
| dc.subject | Missense Variants | |
| dc.subject | CHD1 | |
| dc.subject | Deletion | |
| dc.subject | Neurodevelopment Disorder | |
| dc.subject | Doenças Genéticas | |
| dc.title | Multiple non-contiguous interstitial deletions in 5q21q22.1, including the CHD1 gene, identified in a boy with developmental delay and severe language impairment | eng |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferenceDate | 2025-06-29 | |
| oaire.citation.conferencePlace | Leuven, Belgica | |
| oaire.citation.title | 15th European Cytogenomics Conference (ECA), 29 June-1 July 2025 | |
| oaire.version | http://purl.org/coar/version/c_970fb48d4fbd8a85 |