Clinical comparison of 10q26 overlapping deletions: Delineating the critical region for urogenital anomalies

Abstract

The 10q26 deletion syndrome is a clinically heterogeneous disorder. The most common phenotypic characteristics include pre- and/or postnatal growth retardation, microcephaly, developmental delay/intellectual disability and a facial appearance consisting of a broad nasal bridge with a prominent nose, low-set malformed ears, strabismus, and a thin vermilion of the upper lip. In addition, limb and cardiac anomalies as well as urogenital anomalies are occasionally observed. In this report, we describe three unrelated females with 10q26 terminal deletions who shared clinical features of the syndrome, including urogenital defects. Cytogenetic studies showed an apparently de novo isolated deletion of the long arm of chromosome 10, with breakpoints in 10q26.1, and subsequent oligo array-CGH analysis confirmed the terminal location and defined the size of the overlapping deletions as ∼ 13.46, ∼ 9.31 and ∼ 9.17 Mb. We compared the phenotypic characteristics of the present patients with others reported to have isolated deletions and we suggest that small 10q26.2 terminal deletions may be associated with growth retardation, developmental delay/intellectual disability, craniofacial features and external genital anomalies whereas longer terminal deletions affecting the 10q26.12 and/or 10q26.13 regions may be responsible for renal/urinary tract anomalies. We propose that the haploinsufficiency of one or several genes located in the 10q26.12-q26.13 region may contribute to the renal or urinary tract pathogenesis and we highlight the importance of FGFR2 and probably of CTBP2 as candidate genes.

Novel Unbalanced Translocations Affecting the Long Arms of Chromosomes 10 and 22 Cause Complex Syndromes with Very Severe Neurodevelopmental Delay, Speech Impairment, Autistic Behavior, and Epilepsy

“…Moreover, larger deletions of the 10q distal region (from 10q26.12 to 10qter) have additionally been related to major renal and urinary tract malformations [Yatsenko et al, 2009;Vera-Carbonell et al, 2015]. To our knowledge, autism has not been seen in patients harboring distal 10q deletions.…”

“…Both patients present simultaneously distal monosomy 10q and distal trisomy 22q. An important role of DOCK1 haploinsufficiency in the genetic pathophysiology of distal monosomy 10q syndrome was suspected, as DOCK1 was mapped within the smallest region of overlap among patients affected by this syndrome [Yatsenko et al, 2009;Vera-Carbonell et al, 2015]. DOCK1 was shown to have a role in cell polarity and migration [Hasegawa et al, 1996;Tachibana et al, 2009], and its haploinsufficiency was proposed to cause an impaired maturation and migration of neural progenitors in the developing cortex.…”

Neonate with 10q Interstitial Deletion within the Long Arm of Chromosome 10- A Case Report and Literature Review

“…Most of the neonatal cases that were diagnosed with 10q deletions shortly after birth, had dysmorphic features that prompted testing for genetic abnormalities 2,7,11,17 . Majority of the children in the age group of 1 to 5 years that were diagnosed to have 10q deletions, were originally referred to genetics teams, because of undiagnosed dysmorphic features, and severe developmental delays 3,6,13,17,18 . Unlike adults, there was no strong gender predisposition among pediatric cases 2,8,9,11 .…”

WDR11-mediated Hedgehog signalling defects underlie a new ciliopathy related to Kallmann syndrome

“…There was no disruption of neighboring genes Emx2 and Fgfr2 (Appendix Fig. S1B) that are also located within the 10q26 deletion syndrome region and known to be important in forebrain and genitalia development 15,16 .…”

“…A splice-site mutation in WDR11 has also been found in a combined pituitary hormone deficiency disorder 14 . WDR11 is located within the 600kb minimal microdeletion region associated with the 10q26 deletion syndrome (MIM 609625) 15,16 . WDR11 contains twelve WD domains -minimally conserved motifs of approximately 40 amino acids forming two beta propellers potentially serving as molecular scaffolds 13 .…”