A family case of a rare Xq28 duplication

   Genetic factors contribute to the etiology of intellectual disability in 25–50 % of cases. Chromosomal abnormalities, such as microdeletions and microduplications, are the most significant genetic causes. We examined a family where two boys, aged 8 and 7, were diagnosed with mild intellectual dis...

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Published in:Vavilovskiĭ zhurnal genetiki i selekt͡s︡ii Vol. 29; no. 5; pp. 636 - 643
Main Authors: Kopytova, A. E., Tolmacheva, E. N., Emelina, D. A., Glotov, O. S., Miroshnikova, V. V., Usenko, T. S., Vasilyeva, O. Yu, Kasyanov, E. D., Fonova, E. A., Makarov, I. V., Lobanov, A. D., Mazo, G. E., Pchelina, S. N., Lebedev, I. N.
Format: Journal Article
Language:English
Published: Russia (Federation) Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 01.09.2025
Subjects:
array-based comparative genomic hybridization
clic2
copy number variations (cnvs)
intellectual disability
rab39b
xq28 duplication syndrome
CLIC2For
RAB39B
array-based comparative genomic hybridization
copy number variations (CNVs)
intellectual disability
Xq28 duplication syndrome
ISSN:2500-3259, 2500-0462, 2500-3259
Online Access:Get full text
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Summary:   Genetic factors contribute to the etiology of intellectual disability in 25–50 % of cases. Chromosomal abnormalities, such as microdeletions and microduplications, are the most significant genetic causes. We examined a family where two boys, aged 8 and 7, were diagnosed with mild intellectual disability. Using array-based comparative genomic hybridization, we detected a duplication of Xq28 in both brothers on the X chromosome inherited from a healthy mother with skewed (88 %) X-chromosome inactivation. The size of the rearrangement is 439.6 kilobases (kb). Eight genes are located in this region, including F8, MTCP1, BRCC3, VBP1, RAB39B, CLIC2, FUNDC2, and CMC4. This chromosomal region overlaps with the region of Xq28 duplication syndrome (OMIM 300815), characterized by intellectual disability, behavioral and psychiatric disorders, recurrent infections, atopic diseases, and specific facial features in affected male individuals. Whole-exome sequencing did not reveal pathogenic or likely pathogenic variants associated with neurodevelopmental disorders. These disorders have been previously linked to X-linked recessive single-nucleotide variants in RAB39B (OMIM 300271, 311510) and CLIC2 (OMIM 300886). An assessment of the clinical significance of the identified duplication, using the AutoCNV internet resource and original data, allowed us to classify this variant as pathogenic. This implies that the identified duplication may be the cause of intellectual disability in patients.
ISSN:2500-3259
2500-0462
2500-3259
DOI:10.18699/vjgb-25-69