Molecular and clinical analyses with neuropsychological assessment of a case of del(10)(q26.2qter) without intellectual disability: Genomic and transcriptomic combined approach and review of the literature

Abstract

Terminal deletion of the long arm of the chromosome 10 is a rare but well known abnormality, with a large phenotypic variability. Very few data are available about subtelomeric deletion 10q26 patients without intellectual disability. Herein, we report the case of a young adult with a classical 10q26.2qter deletion. She exhibited mainly short stature at birth and in childhood/adulthood without intellectual disability or behavioral problems. After clinical and neuropsychological assessments, we performed genomic array and transcriptomic analysis and compared our results to the data available in the literature. The patient presents a 6.525 Mb heterozygous 10q26.2qter deletion, encompassed 48 genes. Among those genes, DOCK1, C10orf90, and CALY previously described as potential candidate genes for intellectual disability, were partially or completed deleted. Interestingly, they were not deregulated as demonstrated by transcriptomic analysis. This allowed us to suggest that the mechanism involved in the deletion 10qter phenotype is much more complex that only the haploinsufficiency of DOCK1 or other genes encompassed in the deletion. Genomic and transcriptomic combined approach has to be considered to understand this pathogenesis. © 2016 Wiley Periodicals, Inc.

Neurodevelopmental Impairment As the Main Phenotypic Hallmark Associated with the Translocation t(7;10)(7p22.3;q26.11)

“…Moreover, several cases of 10q deletions without intellectual disability have been reported. 24 All these data seem refusing the hypothesis that DOCK1 can be a dosage-sensitive gene. 24 The hypothesis of a possible gene dosage effect, that could explain the presence of symptoms such as developmental delay or cognitive impairment, autism, epilepsy, or brain malformations, has never been experimentally assessed in the context of 10q26 duplication.…”

“…24 All these data seem refusing the hypothesis that DOCK1 can be a dosage-sensitive gene. 24 The hypothesis of a possible gene dosage effect, that could explain the presence of symptoms such as developmental delay or cognitive impairment, autism, epilepsy, or brain malformations, has never been experimentally assessed in the context of 10q26 duplication. The mild phenotype that was reported in a 11 years old presenting with a moderate intellectual disability and no major malformations and carrying a 10q26!…”

“…The duplicated area in our patient includes 30 genes but only a limited number of them are associated with neuronal functions and development (GRK5, HTRA1, ACADSB, DOCK1, ADAM8, and RGS10). [20][21][22][23][24] Some of these genes have also been previously associated with neurological impairment in patients carrying a deletion on 10q. 20 In particular, DOCK1, that modulates different processes involved in neuronal development (regulation of cell morphology, polarity, migration, proliferation, differentiation, transcription and intercellular communication, apoptosis, vesicular transport, and synaptic release) has been proposed as the most promising candidate gene.…”

Terminal 10q26.12 deletion is associated with neonatal asymmetric crying facies syndrome: a case report and literature review

“…Fourteen OMIM genes are underlined to be morbid genes from DECIPHER database in case of 10q26.12qter deletion (Table 2 ). Several compelling studies reported that interstitial deletion at 10q26.2q26.3 or terminal 10q26.2 deletion only caused mild neurocognitive phenotypes or minor dysmorphic features with near normal development and intellect [ 20 – 23 ]. Therefore, we speculate that the deleted genes located at 10q26.12q26.13 ( OAT , ACADSB, IKZF5, HTRA1, ARMS2, FGFR2 and WDR11 ) are responsible for those notable malformations.…”