9q31.1q31.3 deletion in two patients with similar clinical features: A newly recognized microdeletion syndrome?

Abstract

Interstitial deletions of the long arm of chromosome 9 are rare and most patients have been detected by conventional cytogenetic techniques. Disparities in size and localization are large and no consistent region of overlap has been delineated. We report two similar de novo deletions of 6.3 Mb involving the 9q31.1q31.3 region, identified in two monozygotic twins and one unrelated patient through array-CGH analysis. By cloning the deletion breakpoints, we could show that these deletions are not mediated by segmental duplications. The patients displayed a distinct clinical phenotype characterized by mild intellectual disability, short stature with high body mass index, thick hair, arched eyebrows, flat profile with broad chin and mild prognathism, broad, and slightly overhanging tip of the nose, short neck with cervical gibbus. The twin patients developed a metabolic syndrome (type 2 diabetes, hypercholesterolemia, vascular hypertension) during the third decade of life. Although long-term follow-up and collection of additional patients will be needed to obtain a better definition of the phenotype, our findings characterize a previously undescribed syndromic disorder associated with haploinsufficiency of the chromosome 9q31.1q31.3 region.

A novel familial 9q31.2q32 microdeletion: Muscle cramping, somnolence, fatigue, sensorineural hearing loss, pubertal delay, and short stature

“…Most of these were detected using conventional chromosome banding analysis, and to date, no clear syndrome has been identified). Seven cases have currently been reported using CMA techniques with precise breakpoints that overlap the 9q31.2q32 region . These are represented graphically in Figure and aligned against the deletion seen in our cohort, with a summary of the clinical reports available in Table .…”

“…Kulharya et al reported a patient with a 9q31.1q33.1 deletion (chr9: 111303224‐121018591, hg18) with a phenotype of developmental delay, poor growth, short stature, and dysmorphic facial features. Mucciolo et al described three patients with deletions affecting different breakpoints involving this region. The first had an approximate 6.5 Mb deletion involving chromosome region 9q31.1q31.3 (chr9: 106898551‐113407621, converted to hg18 from hg19) and showed delayed motor milestones, dysmorphic facial features, short stature, cervicothoracic gibbus, and aortic insufficiency.…”

Novel Mutations and Unreported Clinical Features in KBG Syndrome

“…Four individuals were identified through exome sequencing [Tunovic et al, 2014;Posey et al, 2017] and one through targeted sequencing, in a patient who additionally had a de novo deletion of chromosome 9q [Xu et al, 2013]. This last patient nicely exemplifies the need of detailed phenotype analysis because clinical features were felt to be more complex than expected for KBG syndrome, and array CGH identified a rare interstitial deletion described in patients with ID, short stature, and skeletal anomalies [Mucciolo et al, 2014]. In general, the presence of an independent molecular defect poses a significant hurdle to a correct clinical definition.…”

Patients Carrying 9q31.1-q32 Deletion Share Common Features with Cornelia de Lange Syndrome

“…However, reports about the deletion of chromosome 9q are rare and only about 20 patients have been described in medical literature, spanning the breakpoints from 9q21 to 9q34 [10]. To date, no well-defined syndrome has been specifically associated with this region.…”

“…A comparison of our patient with the 11 previously reported cases with partially overlapping deletions is provided in Table 2 and their deletion regions are compared in Fig. 5 (case 1 and case 4 came from DECIPHER, http://decipher.sanger.ac.uk/) [10,11,12,13,14,15,16]. …”