Inverted genomic segments and complex triplication rearrangements are mediated by inverted repeats in the human genome.

We identified complex genomic rearrangements consisting of intermixed duplications and triplications of genomic segments at the MECP2 and PLP1 loci. These complex rearrangements were characterized by a triplicated segment embedded within a duplication in 11 unrelated subjects. Notably, only two breakpoint junctions were generated during each rearrangement formation. All the complex rearrangement products share a common genomic organization, duplication-inverted triplication-duplication (DUP-TRP/INV-DUP), in which the triplicated segment is inverted and located between directly oriented duplicated genomic segments. We provide evidence that the DUP-TRP/INV-DUP structures are mediated by inverted repeats that can be separated by >300 kb, a genomic architecture that apparently leads to susceptibility to such complex rearrangements. A similar inverted repeat-mediated mechanism may underlie structural variation in many other regions of the human genome. We propose a mechanism that involves both homology-driven events, via inverted repeats, and microhomologous or nonhomologous events.

Cleft palate lateral synechia syndrome: an opportunity for unique surgical closure.

OBJECTIVES: To report two cases of cleft palate lateral synechia (CPLS) syndrome in a single family and describe surgical closure using the synechia. STUDY DESIGN: Case report and literature review. METHODS: A case report is presented with a review of the literature of cleft palate in conjunction with lateral synechia. Clinical presentation with photographic images of surgical repair is presented as well as a genetic workup with pedigree. RESULTS: A 6-week-old male presented for evaluation of a cleft palate. Mucosa-lined, fibromuscular tissue bands were noted connecting the floor of mouth and the free edges of a bilateral complete secondary cleft palate. No other craniofacial, digital, genital or limb defects were noted. The patient's 13-month-old sister had similar synechial bands and cleft palate at birth. Another older sibling had cleft palate without synechia. The patient's mother and maternal great grandmother had cleft palates at birth without synechia. The three children share a common mother but have three different fathers. Genetic analysis failed to reveal chromosomal defects or a mutation in the interferon regulatory factor 6 (IRF6) gene, a locus linked to Van der Woude syndrome. At 2 years of age, the index patient was growing and feeding well. His intra-oral bands remained intact and were incorporated in the surgical repair using a novel approach. CONCLUSIONS: Since more otolaryngologists are performing cleft surgeries, the awareness of the differential diagnoses associated with a cleft palate is important. CPLS is an extremely rare condition. The report of this family supports the suspected pattern of autosomal dominant inheritance with variable expressivity. The unusual surgical approach will be discussed.