Concurrent occurrence of an inherited 16p13.11 microduplication and a de novo 19p13.3 microdeletion involving MAP2K2 in a patient with developmental delay, distinctive facial features, and lambdoid synostosis

Abstract

A female patient presented with developmental delay, distinctive facial features, and congenital anomalies, including a heart defect and premature lambdoid synostosis. The patient showed a paternally inherited 16p13.11 microduplication and a de novo 19p13.3 microdeletion involving the mitogen-activated protein kinase kinase 2 gene (MAP2K2), in which mutations cause the cardio-facio-cutaneous (CFC) syndrome. Reports of patients with overlapping 19p13.3 microdeletions of this region describe similar clinical manifestations including distinctive facial features: prominent forehead, horizontal/down-slanting palpebral fissures, long midface, pointed chin/angular jaw, sparse eyebrows, and underdeveloped cheekbones. Some of these findings overlapped to that of the patients with 16p13.11 microduplications and CFC syndrome. Although craniosynostosis was occasionally observed in patients with dominant-negative mutations in RAS/MAP kinase signaling genes (RASopathies) related to CFC syndrome, it was also reported in two patients with 16p13.11 microduplications. Genetic contributions of both chromosomal aberrations were discussed.

A Rare Case of Concomitant Deletions in 15q11.2 and 19p13.3

“…Besides, additional genomic imbalances have been revealed in previous well-defined pathological cases [Vallespin et al, 2013], and rare concomitant rearrangements have been described previously, for example, a sporadic case involving chromosome 19, where the patient presented a de novo 19p13.3 microdeletion and a 16p13.11 microduplication [Shimojima et al, 2016]. Similar to the case cited above, this article describes concomitant rearrangements involving chromosomes 15 and 19.…”

p53 regulates ERK1/2/CREB cascade via a novel SASH1/MAP2K2 crosstalk to induce hyperpigmentation

“…MAP2K2 was initially indentified as an ERK activator from growth factor-treated cells and phosphorylates MAPK1/ERK2 cascade and MAPK2/ ERK3 cascade [18]. A novel c.383C̀->A transversion in exon 3 of MAP2K2 and 19p13.3 microdeletion involving the mitogen-activated protein kinase kinase 2 gene (MAP2K2) were reported to cause the cardio-facio-cutaneous (CFC) syndrome [30,31]. In this study, MAP2K2 is associated with SASH1 to form a novel SASH1/MAP2K2 crosstalk to regulate phosphorylation level of ERK1/2 and CREB, which suggests that SASH1 is involved in MEK/ERK signal cascade (Fig.…”