Proximal 1q21 duplication: A syndrome or a susceptibility locus?

Michal Levy*, Mordechai Shohat, Sarit Kahana, Reut Matar, Kochav Klein, Ifat Agmon Fishman, Merav Gurevitch, Lina Basel-Salmon, Idit Maya

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Proximal 1q21 microduplication is an incomplete penetrance and variable expressivity syndrome. This study reports 28 new cases and summarizes data on phenotype, gender, and parental origin. Data on isolated proximal 1q21.1 microduplications (g. chr1:145,394,956–145,762,959 GRCh37/hg19) was retrieved in postnatal and prenatal “clinical cases” group, and prenatal “control group.” The “clinical cases” cases included cases where chromosomal microarray (CMA) was performed due to congenital anomalies, autism spectrum disorder, seizures, and developmental delay/intellectual disability. The “control group” cases consisted of fetal CMA performed upon parental request despite normal nuchal translucency and anatomical second trimester fetal scans. We analyzed a local database of 27,990 cases and another cohort of 80,000 cases (including both indicated and non-indicated cases) for population frequency analysis. A total of 62 heterozygous cases were found, including 28 index cases and 34 family members. Among the index cases, 13 (9 males, 4 females) were identified in the “clinical cases” group, of which 10 had developmental abnormalities. Parental origin was tested in 9/13 cases, and all were found to be maternally inherited. In the “control group,” which comprised non-affected cases, of 15 cases (10 males, 5 females), only 5/11 were maternally inherited. Four cases with clinical follow-up showed no reported neurodevelopmental abnormalities. No de-novo cases were detected, and the population frequency in both cohorts was 1:1000. Proximal 1q21.1 microduplication is a recurrent copy number variant, associated with neurodevelopmental abnormalities. It has a greater impact on males inheriting it from their mothers than females from their fathers.

Original languageEnglish
Pages (from-to)2551-2557
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Volume191
Issue number10
DOIs
StatePublished - Oct 2023

Keywords

  • genetic counseling
  • postnatal
  • prenatal
  • proximal 1q21.1 microduplication
  • recurrent copy number variant

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