Subtelomeric deletion of chromosome 10p15.3: Clinical findings and molecular cytogenetic characterization

Abstract

We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to date; however, only limited clinical information is available for these probands and the deleted region has not been molecularly mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals described in this study. Common features among these 12 individuals include: cognitive/behavioral/developmental differences (11/11), speech delay/language disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia (7/11,), brain anomalies (4/6) and seizures (3/7). Parental studies were performed for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the probands, not maternally inherited in one proband and inherited from an apparently affected mother in one proband. Molecular mapping of the 19 individuals reported in this study has identified two genes, ZMYND11 (OMIM# 608668) and DIP2C (OMIM# 611380) (UCSC Genome Browser), mapping within 10p15.3 which are most commonly deleted. Although no single gene has been identified which is deleted in all 19 individuals studied, the deleted region in all but one individual includes ZMYND11 and the deleted region in all but one other individual includes DIP2C. There is not a clearly identifiable phenotypic difference between these two individuals and the size of the deleted region does not generally predict clinical features. Little is currently known about these genes complicating a direct genotype/phenotype correlation at this time. These data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to the clinical features associated with 10p15 deletions in probands described in this study.

Importance of genetic testing in global health during the evaluation of familial microcephaly

“…Only two of these 24 cases were microcephalic 2, 4. The other individuals with this deletion have been normocephalic or macrocephalic, indicating that this deletion is probably not the sole cause of the younger daughter's microcephaly.…”

“…This confirmed that the loss at 10p15.3 was de novo and likely clinically significant. Deletions in this region have been reported to be a rare cause of cognitive deficits, speech disorders, motor delay, and hypotonia 2, 3. However, based on previous reports of 10p15.3 deletions, it is unlikely that the deletion fully explains the significant cerebral dysgenesis seen on the brain MRI.…”

Cleft Lip/Palate, Short Stature, and Developmental Delay in a Boy with a 5.6-Mb Interstitial Deletion Involving 10p15.3p14

“…The first condition is associated with haploinsufficiency of the GATA3 gene and the latter with partial monosomy 10p within the DGS2 region [Monaco et al, 1991;Melis et al, 2012]; however, phenotypic heterogeneity has also been noted in several instances [Tremblay et al, 2011;DeScipio et al, 2012].…”

Relatives with Opposite Chromosome Constitutions, rec(10)dup(10p)inv(10)(p15.1q26.12) and rec(10)dup(10q)inv(10)(p15.1q26.12), due to a Familial Pericentric Inversion

“…Pure terminal deletion of chromosome 10p15 has been described in more than 20 unrelated individuals [DeScipio et al, 2012;Vargiami et al, 2014]. Common features among these patients included developmental delay/intellectual disability, craniofacial dysmorphism, hypotonia, brain anomalies, and seizures.…”