Prenatal diagnosis and molecular cytogenetic characterization of a de novo 4.858-Mb microdeletion in 15q14 associated with ACTC1 and MEIS2 haploinsufficiency and tetralogy of Fallot

Abstract

Fetuses with 15q14 microdeletion may present TOF on the second-trimester ultrasound. aCGH and metaphase FISH are useful for rapid prenatal diagnosis of 15q14 microdeletion associated with TOF. A prenatal diagnosis of TOF should include a differential diagnosis of 15q14 microdeletion in addition to 22q11.2 deletion syndrome and other microdeletion syndromes.

Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects, congenital heart defects, and intellectual disability

“…These deletions extend distally from MEIS2 and affect SPRED1, the causal gene for Legius syndrome, which is characterized by multiple café-au-lait macules, intertriginous freckling, lipomas, and learning disabilities [33] (OMIM: 611431). CAL spots were not reported in patients G, K, and N, and the patients described by Chen et al [3,7] and by Brunetti-Pieri et al [2], although the deletions in these patients encompass SPRED1. This could be attributed to young age at diagnosis, variable expressivity, or inaccurate phenotyping.…”

“…Decipher patient 286841, as well as the six patients reported recently by Gambin et al [9], were excluded from further genotype-phenotype analysis, as no sufficient clinical features could be retrieved (supplementary table 3). Twentyfive deletion carriers from 24 independent families were retained (patients A to N and 11 previously reported families [1][2][3][4][5][6][7][8]) (Table 2 and supplementary table 2). All 24 deletions affected the gene MEIS2, either completely (14/ 24), or partially (10/24).…”

“…It is currently unclear whether this partial CTNND2 duplication occurred in tandem, and whether it contributed to the patient's phenotype. In patient C a de novo deletion on chromosome 12q23.3 Autism (4) Autism (7) was identified (chr12:g.(?_108249783)_(108711392_?)del). This deletion is absent from patient and normal population databases and affects two genes (WSCD2 and CMKLR1), which are not yet linked to developmental disorders.…”

“…Deletions on chromosome 15q14 are a known chromosomal cause of cleft palate, typically co-occurring with intellectual disability (ID), facial dysmorphism and congenital heart defects (CHD) [1][2][3][4][5][6][7][8][9]. De novo loss-of-function variants in MEIS2, a gene within this region, were previously described in two patients with CP, ID, and CHD [10,11].…”

A 15q14 microdeletion involving MEIS2 identified in a patient with autism spectrum disorder

“…The clinical features of this patient are summarized in Table 1 and are compared with those of the previously reported patients with 15q14 deletions 4,5,6, 7,8 and MEIS2 mutations. 1,2 As shown, various degrees of developmental delay are commonly observed in the patients with MEIS2 haploinsufficiency.…”