Tetrasomy 9p Mosaicism Associated with a Normal Phenotype

Abstract

Isochromosome (tetrasomy) 9p is a rare chromosomal aberration characterized by phenotypic abnormalities ranging from mild developmental delay to multiple anomalies including intrauterine growth retardation, cerebral ventriculomegaly, dysmorphic facial features, cleft lip or palate, abnormal genitalia and renal anomalies. We present a patient with isochromosome (tetrasomy) 9p mosaicism who is a healthy normal adult male with oligospermia who has fathered two normal children. This chromosomal abnormality may be tissue specific, with a higher detection rate in cultured lymphocytes compared with fibroblasts. Therefore, there is an increased chance of missing the abnormality prenatally by amniocentesis or chorionic villus sampling. We are aware of only one other patient in the literature with a normal phenotype associated with mosaicism for this chromosomal abnormality.

Mosaic Tetrasomy 9p: A Mendelian Condition Associated With Pediatric-Onset Overlap Myositis

“…However, normal phenotypes are also possible. [6][7][8] This report identifies, for the first time to our knowledge, mosaic tetrasomy of 9p as predisposing to the development of IM, which is associated with an upregulation of type I IFN activity.…”

Prenatal diagnosis and findings of tetrasomy 9p

“…In a recent case reported by Shehab et al ., karyotype analysis of peripheral blood lymphocytes detected a supernumerary isochromosome 9p present in every cell, with the initial result being reported as tetrasomy 9p in non‐mosaic form. However, array comparative genomic hybridization (aCGH) studies on DNA extracted from peripheral blood lymphocytes and saliva showed that the patient had tissue‐specific mosaicism, with a lower level of abnormal cells in the saliva, further supporting the fact that missing the abnormality prenatally by amniocentesis or chorionic villus sampling is a concern . Yet a case of prenatally diagnosed low‐level mosaic (mos 47,XX,+idic(9)(pter → q12:q12 → pter)[4]/46,XX[16]) by amniocentesis has been previously reported .…”

“…In peripheral blood, the isochromosome is often found in all, or a very high proportion of cells, whereas in fibroblasts, amniotic fluid and chorionic villi, it is present in a lower proportion of cells, or not at all . Therefore, missing the abnormality prenatally by amniocentesis or chorionic villus sampling is a concern . This contrasts with other mosaic chromosome abnormalities, such as Pallister–Killian syndrome, where the isochromosome 12p is present at a higher frequency in fibroblasts than in peripheral blood cells …”

Tetrasomy 9p Mosaicism Associated with a Normal Phenotype in Two Cases

“…There are 3 patients depicted in the literature with mosaicism for isochromosome 9p and a normal phenotype [Sait and Wetzler, 2003;McAuliffe et al, 2005;Baronchelli et al, 2011] ( table 1 ). Sait and Wetzler [2003] described a healthy 41-year-old male with mosaicism of isochromosome 9p who was referred for cytogenetic analysis because of skin lesions; the only abnormality found was hypereosinophilia in the bone marrow and peripheral blood film.…”

“…sSMCs are structurally abnormal chromosomes that cannot be identified or characterized unambiguously by conventional cytogenetics alone, and they are generally equal in size or smaller than chromosome 20 of the same metaphase spread [Liehr et al, 2004]. To date, only one report is available for a triple-X syndrome patient with an additional sSMC [Lee-Jones et al, 2004], and only 3 cases have been reported so far with mosaic tetrasomy 9p that present no clinical symptoms [Sait and Wetzler, 2003;McAuliffe et al, 2005;Baronchelli et al, 2011].…”