Interstitial deletion of 5q33.3q35.1 in a boy with severe mental retardation

Abstract

Constitutional interstitial deletions of the long arm of chromosome 5 (5q) are quite rare, and the corresponding phenotype is not yet clearly delineated. Severe mental retardation has been described in most patients who present 5q deletions. Specifically, the interstitial deletion of chromosome 5q33.3q35.1, an extremely rare chromosomal aberration, is characterized by mental retardation, developmental delay, and facial dysmorphism. Although the severity of mental retardation varies across cases, it is the most common feature described in patients who present the 5q33.3q35.1 deletion. Here, we report a case of a de novo deletion of 5q33.3q35.1, 46,XY,del(5)(q33.3q35.1) in an 11-year-old boy with mental retardation; to the best of our knowledge this is the first case in Korea to be reported. He was diagnosed with severe mental retardation, developmental delay, facial dysmorphisms, dental anomalies, and epilepsy. Chromosomal microarray analysis using the comparative genomic hybridization array method revealed a 16-Mb-long deletion of 5q33. 3q35.1(156,409,412-172,584,708)x1. Understanding this deletion may help draw a rough phenotypic map of 5q and correlate the phenotypes with specific chromosomal regions. The 5q33.3q35.1 deletion is a rare condition; however, accurate diagnosis of the associated mental retardation is important to ensure proper genetic counseling and to guide patients as part of long-term management.

De novo hotspot variants in CYFIP2 cause early‐onset epileptic encephalopathy

“…This individual showed developmental delay, mild intellectual disability, minor facial anomalies, seizures, and behavioral problems . A boy with a 16‐Mb deletion at 5q33.3 to q35.1 showed developmental delay, severe intellectual disability, facial dysmorphisms, teeth agenesis, and seizures . Both individuals shared common clinical features, including developmental delay, cognitive impairment, seizures, and facial dysmorphism.…”

“…To date, 2 individuals with a de novo 5q33.3 to q35.1 deletion involving CYFIP2 have been reported . In 1 girl, a de novo 5q33.3q35.1 deletion was detected by two‐color fluorescence in situ hybridization, but the deletion size was not characterized.…”

“…Some evidence has suggested possible involvement of CYFIP2 abnormalities in neurodevelopmental disorders. Interstitial deletions at 5q33.3 to q35.1 encompassing CYFIP2 have been found in two individuals with intellectual disability, seizures, and craniofacial dysmorphic features . Recent studies using next‐generation sequencing for neurodevelopmental disorders also have identified some de novo variants in CYFIP2 .…”

Haploinsufficiency of Cyfip2 Causes Lithium‐Responsive Prefrontal Dysfunction

“…Based on the hyperexcitability of Cyfip2 +/− neurons, we investigated the seizure susceptibility of Cyfip2 +/− mice, which might potentially be implicated in epilepsy commonly seen in patients with CYFIP2 deletions and missense variants 5,7–10 . We induced seizures in mice by injecting PTZ and assessed seizure behaviors.…”

“…Specifically, deletions and duplications of CYFIP1 , which is located within the 15q11.2 breakpoints BP1–BP2 of the Angelman/Prader–Willi syndrome region, 3 are associated with intellectual disability (ID), autism spectrum disorders (ASDs), and schizophrenia (SCZ) 2,4 . Regarding CYFIP2 , interstitial deletions of the chromosomal region 5q33.3–q35.1 harboring CYFIP2 (ie, haploinsufficiency) were identified in individuals with developmental delay, mild to severe ID, and seizures 5,6 . Moreover, recent whole‐exome and whole‐genome sequencing studies identified de novo CYFIP2 missense variants in patients with developmental delay, early‐onset epileptic encephalopathy, and severe ID 7–10 …”