Novel 14q11.2 microduplication including the CHD8 and SUPT16H genes associated with developmental delay

Abstract

Neurodevelopmental disorders have long been associated with chromosomal abnormalities, including microdeletions and microduplications. Submicroscopic 14q11.2 deletions involving the CHD8 and SUPT16H genes have been reported in patients with developmental delay (DD)/intellectual disability (ID) or autism spectrum disorders (ASDs) and/or macrocephaly. Recently, disruptive CHD8 mutations were described in patients with similar phenotypes further showing pivotal role of CHD8 gene in the pathogenesis of DD/ID or ASDs. We report here the first case of ~445 kb de novo microduplication, encompassing the minimal critical 14q11.2 deletion region, in 8-year-old boy showing DD, cognitive impairment and facial dysmorphism. Our results suggest that gain of the chromosomal region 14q11.2 is causative for clinical findings present in the patient.

De novo variants in SUPT16H cause neurodevelopmental disorders associated with corpus callosum abnormalities

“…No reports prior to this study linked SUPT16H to NDD. However, microdeletions and duplications of 14q11.2 are reported to be associated with ID (intellectual disability), ASD (autism spectrum disorder), macrocephaly and minor dysmorphic features 17–19. For CNV deletions previously reported in this region, CHD8 and SUPT16H have been proposed as the two candidate genes (as these two genes were the only ones found in a minimal critical region in this interval).…”

Prenatal diagnosis of maternal partial trisomy 9p23p24.3 and 14q11.2q21.3 in a fetus: a case report

“…That was to say, the fetus not only inherited the normal chromosomes 9 and 14 of the parents', but also had a derived abnormal chromosome 14 from the mother. Trisomy 9p was the fourth most frequent chromosome anomaly compatible with long-term survival in live-born infants [13,14,34], meanwhile trisomy 14q was not less than reported trisomy 9p in the literatures of 1970s [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]35]. However, the case of partial 9p and 14q trisomy has been reported only once to date [1].…”

“…A 14-year-old male patient with a de novo 14q11.2 microduplication, a region significantly associated with quantitative trait loci for stature and a component of intelligence, was significantly characterized by short stature, mild mental retardation, Table 1 and dysmorphic facial features [30]. A 445-kb 14q11.2 microduplication involving CHD8 and SUPT16H genes causes developmental delay, intellectual disability, autism spectrum disorders, and macrocephaly, which was found in an 8-year-old boy [31]. The clinical phenotype of 14q11.2 microduplication included postpartum slow growth, microcephalus, abnormal breathing patterns, gastroesophageal reflux, dysgnosia, and agenesis of the corpus callosum [5,30].…”

“…The clinical phenotype of 14q11.2 microduplication included postpartum slow growth, microcephalus, abnormal breathing patterns, gastroesophageal reflux, dysgnosia, and agenesis of the corpus callosum [5,30]. The PRKD1 gene mutations are associated with autosomal dominant diseases, including congenital heart defects and ectodermal dysplasia [30,31]. Furthermore, the thickness of the fetal nuchal translucency in the present case was 3.5 mm, and the heart had an approximately 1.0-mm ventricular defect detected during ultrasound examination at 12-week gestation, which might have been caused by the PRKD1 gene mutation.…”

Familial reciprocal non robertsonian translocation t(14;22) resulting in 22q11.2 deletion syndrome

“…Clinically 22q11.2 deletions and 14pter-q12~13 duplications share common features including developmental delay, mild dysmorphic features, recurrent infections and congenital heart disease (CHD) Table I. 6,10,[12][13]15 Aside from CHD absent in patient 1, the 2 patients shared the aforementioned features. Our patients showed phenotypic variability previously reported in patients exhibiting 22q11.2 deletions.…”