Contiguous ∼16 Mb 1p36 deletion: Dominant features of classical distal 1p36 monosomy with haplo‐lethality

• Published in: American journal of medical genetics. Part A 2011-08, Vol.155 (8), p.1964-1968
• Main Authors: Nicoulaz, A., Rubi, F., Lieder, L., Wolf, R., Goeggel‐Simonetti, B., Steinlin, M., Wiest, R., Bonel, H.M., Schaller, A., Gallati, S., Conrad, B.
• Format: Article
• Language: English
• Subjects: 1p36 monosomy; Abnormalities, Multiple - genetics; Agenesis of Corpus Callosum; array‐CGH; Brain Diseases - genetics; Chromosome Breakpoints; Chromosome Deletion; Chromosome Disorders - diagnosis; Chromosome Disorders - genetics; Chromosomes, Human, Pair 1 - genetics; Comparative Genomic Hybridization; critical distal 1p36.33 region; Fatal Outcome; Female; Gene Deletion; Genetic Association Studies; haplo‐lethality; Humans; Infant, Newborn; neuronal migration disorders; Phenotype; Polyhydramnios - diagnosis; Pregnancy; Premature Birth; Respiratory Insufficiency - diagnosis; Septum Pellucidum - abnormalities
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.33210

Monosomy 1p36 results from heterozygous deletions of the terminal short chromosome 1 arm, the most common terminal deletion in humans. The microdeletion is split in two usually non‐overlapping and clinically distinct classical distal and proximal 1p36 monosomy syndromes. Using comparative genome hybridization, MLPA and qPCR we identified the largest contiguous ∼16 Mb terminal 1p36 deletion reported to date. It covers both distal and proximal regions, causes a neonatally lethal variant with virtually exclusive features of distal 1p36 monosomy, highlighting the key importance of the gene‐rich distal region for the “compound” 1p36 phenotype and a threshold deletion‐size effect for haplo‐lethality. © 2011 Wiley‐Liss, Inc.