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Status |
Public on Jun 01, 2020 |
Title |
Compound craniosynostosis, intellectual disability and Noonan-like facial dysmorphism associated with 7q32.3-q35 deletion |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Craniosynostosis (CS) is the premature fusion of the cranial sutures,occurring either in isolated or syndromic form. CS was described in over 180 genetic syndromes that comprise 15-30% of all CS cases. Syndromic CS usually has a monogenic inheritance and originates in most of the patients from mutations within the FGFR1, FGFR2, FGFR3, and TWIST1 genes. Causative alterations in other genes, or rarely copy number variations (CNVs) were also reported. In this paper, we describe a patient with Noonan-like facial dysmorphism accompanied by intellectual disability, and compound CS, involving coronal, sagittal, and squamous sutures. We have shown that the index carried a large and rare heterozygous deletion, which encompassed 12.782 Mb and mapped to a chromosomal region of 7q32.3-q35 (HG38 – chr7:131837067-144607071). The aberration comprised 109 protein-coding genes, including BRAF, that encodes serine/threonine-protein kinase B-Raf, being a part of the RAS/MAPK signaling pathway. The RAS/MAPK pathway plays an essential role in human development, hence its dysregulation not surprisingly results in severe congenital anomalies, such as phenotypically overlapping syndromes termed RASopathies. To our best knowledge, we report here the first CNV causing haploinsufficiency of BRAF, resulting in dysregulation of the RAS/MAPK cascade, and consequently, in the phenotype observed in our patient. To conclude, with this report, we have pointed to the involvement of the RAS/MAPK signaling pathway in CS development. Moreover, we have shown that the molecular analysis based on both DNA and RNA profiling, undoubtedly constitutes a comprehensive diagnostic and research strategy for elucidating a cause of genetic diseases.
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Overall design |
female control and female patient
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Contributor(s) |
Bukowska-Olech E |
Citation missing |
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Submission date |
May 18, 2020 |
Last update date |
Jun 03, 2020 |
Contact name |
Ewelina Bukowska-Olech |
E-mail(s) |
ewelina.bukowska-olech@student.ump.edu.pl
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Organization name |
Univeristy of Medical Sciences
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Street address |
Rokietnicka 8
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City |
Poznan |
ZIP/Postal code |
60-806 |
Country |
Poland |
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Platforms (1) |
GPL20844 |
Agilent-072363 SurePrint G3 Human GE v3 8x60K Microarray 039494 [Feature Number Version] |
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Samples (2) |
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Relations |
BioProject |
PRJNA633506 |
Supplementary file |
Size |
Download |
File type/resource |
GSE150754_RAW.tar |
16.3 Mb |
(http)(custom) |
TAR (of TXT) |
Processed data included within Sample table |
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