Genotypic and phenotypic variability of 22q11.2 microdeletions - an institutional experience.

Patients with chromosome 22q11.2 deletion syndromes classically present with variable cardiac defects, parathyroid and thyroid gland hypoplasia, immunodeficiency and velopharyngeal insufficiency, developmental delay, intellectual disability, cognitive impairment, and psychiatric disorders. New technologies including chromosome microarray have identified smaller deletions in the 22q11.2 region. An increasing number of studies have reported patients presenting with various features harboring smaller 22q11.2 deletions, suggesting a need to better elucidate 22q11.2 deletions and their phenotypic contributions so that clinicians may better guide prognosis for families. We identified 16 pediatric patients at our institution harboring various 22q11.2 deletions detected by chromosomal microarray and report their clinical presentations. Findings include various neurodevelopmental delays with the most common one being attention deficit hyperactivity disorder (ADHD), one reported case of infant lethality, four cases of preterm birth, one case with dual diagnoses of 22q11.2 microdeletion and Down syndrome. We examined potential genotypic contributions of the deleted regions.

Phenotypes Associated with 16p11.2 Copy Number Gains and Losses at a Single Institution.

Chromosome 16p11.2 is one of the susceptible sites for recurrent copy number variations (CNVs) due to flanking near-identical segmental duplications. Five segmental duplications, named breakpoints 1 to 5 (BP1-BP5), have been defined as recombination hotspots within 16p11.2. Common CNVs on 16p11.2 include a proximal ~593 kb between BP4 and BP5, and a distal ~220 kb between BP2 and BP3. We performed a search for patients carrying 16p11.2 CNVs, as detected using chromosome microarray (CMA), in the Molecular Diagnostic Laboratory at the University of Texas Medical Branch (UTMB), in Galveston. From March 2013 through April 2018, a total of 1200 CMA results were generated for germline testing, and 14 patients tested positive for 16p11.2 CNVs, of whom 7 had proximal deletion, 2 had distal deletion, 4 had proximal duplication, and 1 had distal duplication. Herein, we provide detailed phenotype data for these patients. Our study results show that developmental delay, abnormal body weight, behavioral problems, and hypotonia are common phenotypes associated with 16p11.2 CNVs.

Genotypic and phenotypic variability of 22q11.2 microduplications: An institutional experience.

Duplications in the 22q11.2 region can cause 22q11.2 duplication syndrome and encompass a variety of phenotypes including developmental delays, facial abnormalities, cardiovascular defects, central nervous system delays, and other congenital abnormalities. However, the contribution of these contiguous duplicated regions to the clinical phenotypes has not been fully elucidated. In this study, we identified nine patients carrying different 22q11.2 microduplications detected by chromosomal microarray. Of these patients, seven pediatric patients presented with various clinical features including two neonate cases died shortly after birth, and two healthy adults. We examined region specific genotype-phenotype associations and found unpredictability associated with 22q11.2 duplications in these nine patients.

Subtelomeric rearrangements in idiopathic mental retardation.

OBJECTIVE: To estimate the frequency of subtelomeric rearrangements in patients with sporadic and non-syndromic idiopathic mental retardation (IMR). METHODS: A total of 18 IMR patients were taken for the study. Selection criteria included no known syndromes or chromosomes abnormalities and known causes of IMR. All patients signed an informed consent to participate. Chromosome analysis was carried out on all patients to rule out gross chromosome abnormalities. Lymphocyte cultures were initiated and harvested using standard protocols. For fluorescence in situ hybridization (FISH), Chromoprobe Multiprobe-T system was used. This system consists of 24 embossed areas with each area having one reversibly bound subtelomere probe for a specific chromosome. The subtelomere probes were differentially labeled with green fluorescence for short arm and orange for the long arm. Hybridization, washing and staining are done using standard protocols. A minimum of 5 metaphases were analyzed per chromosome per patient. RESULTS: A total of 2 subtelomeric rearrangements were detected (11.1%). Case 1 involved a 17-year-old with severe MR, profound deafness and dysmorphic features with reciprocal translocation t(3;7)(q26.2; p15.1). The second case involved a 4.6-year-old with mild developmental delay and a terminal deletion of the long arm of chromosome 2, del(2) (q37.3). The frequency of abnormalities detected in our study is in agreement with published reports. CONCLUSION: Subtelomeric screening with FISH is a useful tool for investigation of IMR, however, it is not cost effective in all cases. Conventional chromosome analysis coupled with targeted FISH testing might be the optimal strategy for investigation of IMR.