invdup(8)(8q24.13q24.3)-A Complex Alteration and Its Clinical Consequences

Abstract

Structural variation is a source of genetic variation that, in some cases, may trigger pathogenicity. Here, we describe two cases, a mother and son, with the same partial inverted duplication of the long arm of chromosome 8 [invdup(8)(q24.21q24.21)] of 17.18 Mb, showing different clinical manifestations: microcephaly, dorsal hypertrichosis, seizures and neuropsychomotor development delay in the child, and a cleft lip/palate, down-slanted palpebral fissures and learning disabilities in the mother. The deleterious outcome, in general, is reflected by the gain or loss of genetic material. However, discrepancies among the clinical manifestations raise some concerns about the genomic configuration within the chromosome and other genetic modifiers. With that in mind, we also performed a literature review of research published in the last 20 years about the duplication of the same, or close, chromosome region, seeking the elucidation of at least some relevant clinical features.

Keywords: chromosome 8; cleft lip/palate; duplication; inversion; neuropsychomotor development delay.

Figure 1

Patient and his mother. (A) Frontal photo of the patient. (B) Lateral photo of the patient. (C) Frontal photo of the patient’s mother. (D) Lateral photo of the patient’s mother.

Figure 2

Patient’s pedigree chart. Arrow indicates the index case with neuropsychomotor development delay; Black quarter on the left: cleft lip; Black quarter on the right: cleft palate; Half black: cleft lip and palate; Black spot: learning disability. The age of death or gestacional period is indicated below each individual; y: year; m: month.

Figure 3

GTG banding karyotype and FISH from the index case [7] and his parents. On the right, ideograms of chromosome 8 with the probe signals and representation of the mother’s meiotic pairing. Red: probe labeling the gene MYC; Green: probe labeling the gene GSDMC; Blue arrows: representation of gene BAI1.

Figure 4

Schematic comparison of the duplicated regions of our patient and his mother with other described cases. The position and size of each gene are represented by the yellow (duplication) or purple (deletion) bars. Some of the smaller genes are not represented. A full gene description can be found in Table S1. The hatched portion of the bar marks the uncertain included region. Red: MYC gene, green: GSCMC gene and blue: BAI1 gene [2,3,9,10,11,12,13,14,15].