Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in etiology of ACDMPV.

Delayed ambulation after hip fracture surgery is related to the development of new onset delirium and pneumonia postoperatively as well as to increased length of hospital stay. Early ambulation after hip fracture surgery should be encouraged.

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Highlights Assessment of clinically significant copy number alterations (CNAs) and copy-neutral loss-of-heterozygosity (CN-LOH) in myeloid malignancies by chromosomal microarray (CMA) can improve diagnostic yield, refine risk-stratification and provide genomic information to guide therapy. The Cancer Genomics Consortium (CGC) Working Group for Myeloid Neoplasms performed an extensive systematic examination of the peerreviewed literature to evaluate the clinical value of CMA testing in the workup of myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and myeloproliferative neoplasms (MPN). Based on the evidence, this review describes the specific clinical scenarios where CMA can complement the information obtained by current standard-of-care testing modalities. An example of a testing algorithm illustrating how CMA can be incorporated in selected settings within the backbone of the current testing guidelines is provided. In addition, the current review provides an exhaustive list of recurrent CNAs and CN-LOH observed in these myeloid neoplasms and their clinical significance.

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