A Recurrent De Novo Terminal Duplication of 14q32 in Korean Siblings Associated with Developmental Delay and Intellectual Disability, Growth Retardation, Facial Dysmorphism, and Cerebral Infarction: A Case Report and Literature Review

Abstract

The terminal 14q32 duplication has been reported often in association with other cytogenetic abnormalities, and individuals with this specific duplication showed varying degrees of developmental delay/intellectual disability (DD/ID) and growth retardation (GR), and distinct facial dysmorphisms. Herein, based on the limited cases of terminal duplication of 14q32 known to date, we present new affected siblings presenting with DD/ID, GR, and facial dysmorphism, as well as cerebral infarction caused by recurrent de novo der(14)t(14;14)(p11.2;q32.1) leading to terminal duplication of 14q32. We used coverage analysis generated via duo exome sequencing, performed chromosomal microarray (CMA) as a confirmatory test, and compared our findings with those reported previously. Coverage analysis generated via duo exome sequencing revealed a 17.2 Mb heterozygous duplication at chromosome 14q32.11-q32.33 with a Z ratio ranging between 0.5 and 1 in the proband and her elder brother. As a complementary method, CMA established a terminal duplication described as the arr[hg19]14q32.11q32.33(90,043,558_107,258,824)x3 in the proband and her elder brother; however, the parents and other siblings showed normal karyotyping and no abnormal gain or loss of CMA results. Five candidate genes, BCL11B, CCNK, YY1, DYNC1H1, and PACS2, were associated with the clinical phenotypes in our cases. Although the parents had normal chromosomes, two affected cases carrying terminal duplication of 14q32 can be explained by gonadal mosaicism. Further studies are needed to establish the association between cerebrovascular events and terminal duplication of chromosome 14q32, including investigation into the cytogenetics of patients with precise clinical descriptions.

Initial clinical and molecular investigation of 20q13.33 microdeletion with 17q25.3/14q32.31q32.33 microduplication in Chinese pediatric patients

“…However, the authors are more inclined to consider that the microdeletion of 14q32.33 is responsible for the abnormal white matter observed on MRI. Despite the identification of a 14q32.11q32.33 microduplication covering BCL11B, CCNK, YY1, DYNC1H1, and PACS2 candidate genes in a patient with developmental delay, intellectual disability, and facial dysmorphism (Han & Park, 2021), in the present report, CNVs were found to contain DYNC1H1 and PACS2 genes as well. Pathogenic mutations in PACS2 are associated with developmental and epileptic encephalopathy 66 (Olson et al, 2018).…”

Microdeletions and microduplications linked to severe congenital disorders in infertile men

“…He also presented obesity (BMI > 30) and height (170 cm) that was over 10 cm below the average male height in the Estonian population (181–182 cm) 2 . The patient SO1 also carried a subtelomeric non-recurrent 14q32.33 microduplication (1.2 Mb), recently linked to DD/ID 35 . The carriership of both large CNVs was externally validated by aCGH (Methods, Fig.…”

18q21.1q21.32 Deletion in a Patient With Juvenile Cerebral Infarction

“…To date, cases of juvenile cerebral infarction have been reported in patients with various numerical and structural chromosomal aberrations [1][2][3][4][5]. Some of these cases have thrombus-related genes within chromosomal aberration regions, such as the VWF gene encoding von Willebrand factor and the SERPINC1 gene encoding antithrombin [1,2]; however, in others, the association between chromosomal aberrations and cerebral infarction remains unclear.…”