Details

Autor(en) / Beteiligte

• Xavier, Jean
• Zhou, Bo
• Bilan, Frédéric
• Zhang, Xianglong
• Gilbert-Dussardier, Brigitte
• Viaux-Savelon, Sylvie
• Pattni, Reenal
• Ho, Steve S
• Cohen, David
• Levinson, Douglas F
• Urban, Alexander E
• Laurent-Levinson, Claudine

Titel

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

Ist Teil von

• Npj genomic medicine, 2018-08, Vol.3 (1), p.24-6, Article 24

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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). has been hypothesized to underlie macrocephaly and perhaps cognitive deficits in this syndrome, but assessment of copy number by microarray is difficult because of extensive segmental duplications. We performed whole-genome sequencing which supported duplication (chr1:146,370,001-148,590,000, 2.22 Mb, hg38). To evaluate copy number more rigorously we developed droplet digital PCR assays of (targeting unique 1 kb and 6 kb insertions) and its paralog (targeting a unique 154 bp segment outside the overlap). In an independent cohort, ddPCR was concordant with previous microarray data. Duplication of was confirmed in the patient by ddPCR. This case demonstrates that a large discrepancy of verbal and non-verbal abilities can occur in 1q21.1 duplication syndrome, but it remains unclear whether this has a specific genomic basis. These ddPCR assays may be useful for future research on copy number.