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

Abstract

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.

Recurrence risks for different pregnancy outcomes and meiotic segregation analysis of spermatozoa in carriers of t(1;11)(p36.22;q12.2)

“…7,16 Our observation confirms two previous suggestions of Saito et al 37 and Nicoulaz et al 35 that 1p36 region for pure distal terminal deletions, 411 Mb is the haplolethal. Although many large 1p36 deletions~10-11 Mb in size are likely nonlethal, 39,[42][43][44] additional observations are necessary to determine if monosomy 1p36-pter sized 411 Mb is risk factor for limited survival rate.…”

“…The size of the imbalance is variable with 1p36 deletions arising de novo or resulting from malsegregation of a parental RCT. [38][39][40][41] The clinical findings in our pedigrees of neonatal have been reported with monosomy 1p36 19,32,34,35,38,[40][41][42] as well as reported with trisomy 11q13. 26 Monosomy of 1p36 of~16 Mb in size was described by Nicoulaz et al 35 in a child born at 31 week of gestation who passed away at 48 h after delivery.…”

Mini-Review Monosomy 1p36 syndrome: reviewing the correlation between deletion sizes and phenotypes

“…Deletions ranging from 199 kb to 16 Mb have been previously reported (Rosenfeld et al, 2010;Nicoulaz et al, 2011). Patients bearing 1p36 deletions of different sizes have been shown to express similar phenotypes.…”

“…Among these, 17 scientific articles met the criteria for inclusion and were selected for this study (D'Angelo et al, 2006;Krepischi-Santos et al, 2006;Kang et al, 2007;Robinson et al, 2008;Bursztejn et al, 2009;El-Hattab et al, 2010;Gajecka et al, 2010;Rosenfeld et al, 2010;Haimi et al, 2011;Mikhail et al, 2011;Nicoulaz et al, 2011;Giannikou et al, 2012;Gervasini et al, 2013;Shiba et al, 2013;Zhu et al, 2013;Shimada et al, 2014;Stagi et al, 2014). Among these, 12 were case reports and five reported series of cases.…”

“…On the other hand, the patient showing the largest chromosomal loss (16 Mb) featured deep eyes, skeletal, gastrointestinal, cardiac and cerebral abnormalities, prenatal growth delay, polyhydramnios, and increased nuchal translucency (Nicoulaz et al, 2011).…”