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Recurrent interstitial 1p36 deletions: Evidence for germline mosaicism and complex rearrangement breakpoints
Author(s) -
Gajecka Marzena,
Saitta Sulagna C.,
Gentles Andrew J.,
Campbell Lindsey,
Ciprero Karen,
Geiger Elizabeth,
Catherwood Anne,
Rosenfeld Jill A.,
Shaikh Tamim,
Shaffer Lisa G.
Publication year - 2010
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33733
Subject(s) - biology , subtelomere , breakpoint , monosomy , genetics , fluorescence in situ hybridization , germline , germline mosaicism , comparative genomic hybridization , chromosomal rearrangement , haploinsufficiency , gene rearrangement , karyotype , chromosome , phenotype , gene
Deletions of chromosome 1p36 are one of the most frequently encountered subtelomeric alterations. Clinical features of monosomy 1p36 include neurocognitive impairment, hearing loss, seizures, cardiac defects, and characteristic facial features. The majority of cases have occurred sporadically, implying that genomic instability plays a role in the prevalence of the syndrome. Here, we report two siblings with mild phenotypic features of the deletion syndrome, including developmental delay, hearing loss, and left ventricular non‐compaction (LVNC). Microarray analysis using bacterial artificial chromosome and oligonucleotide microarrays indicated the deletions were identical, suggesting germline mosaicism. Parental phenotypes were normal, and analysis by fluorescence in situ hybridization (FISH) did not show mosaicism. These small interstitial deletions were not detectable by conventional subtelomeric FISH analysis. To investigate the mechanism of deletion further, the breakpoints were cloned and sequenced, demonstrating the presence of a complex rearrangement. Sequence analysis of genes in the deletion interval did not reveal any mutations on the intact homologue that may have contributed to the LVNC seen in both children. This is the first report of apparent germline mosaicism for this disorder. Thus, our findings have important implications for diagnostic approaches and for recurrence risk counseling in families with a child with monosomy 1p36. In addition, our results further refine the minimal critical region for LVNC and hearing loss. © 2010 Wiley‐Liss, Inc.