1q21.1 microduplication: large verbal-nonverbal performance discrepancy and ddPCR assays of HYDIN/HYDIN2 copy number

NPJ Genomic Medicine
Jean XavierClaudine Laurent-Levinson

Abstract

Microduplication of chromosome 1q21.1 is observed in ~0.03% of adults. It has a highly variable, incompletely penetrant phenotype that can include intellectual disability, global developmental delay, specific learning disabilities, autism, schizophrenia, heart anomalies and dysmorphic features. We evaluated a 10-year-old-male with a 1q21.1 duplication by CGH microarray. He presented with major attention deficits, phonological dysphasia, poor fine motor skills, dysmorphia and mild autistic features, but not the typical macrocephaly. Neuropsychiatric evaluation demonstrated a novel phenotype: an unusually large discrepancy between non-verbal capacities (borderline-impaired WISC-IV index scores of 70 for Working Memory and 68 for Processing Speed) vs. strong verbal skills - scores of 126 for Verbal Comprehension (superior) and 111 for Perceptual Reasoning (normal). HYDIN2 has been hypothesized to underlie macrocephaly and perhaps cognitive deficits in this syndrome, but assessment of HYDIN2 copy number by microarray is difficult because of extensive segmental duplications. We performed whole-genome sequencing which supported HYDIN2 duplication (chr1:146,370,001-148,590,000, 2.22 Mb, hg38). To evaluate copy number more rigorously w...Continue Reading

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Methods Mentioned

BETA
PCR

Software Mentioned

CNVnator
Birdsuite
HYDIN
Integrative Genomics Viewer
Affymetrix

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