Molecular cytogenetic characterisation of an interstitial deletion 12p detected by prenatal diagnosis

Abstract

The presented case shows the power of modern cytogenetic methods, allowing a more detailed diagnosis in affected individuals, and therefore, facilitating a more reliable prenatal diagnosis.

A 10.46 Mb 12p11.1–12.1 interstitial deletion coincident with a 0.19 Mb NRXN1 deletion detected by array CGH in a girl with scoliosis and autism

“…These patients' clinical phenotype are summarized in Table I. In general, it is difficult to distinguish clinical hallmarks of this small sub-group from the other patients because clinical symptoms of all patients are too unspecific to generate a specific phenotype for the deletion 12p patients [Stumm et al, 2007]. The first published report about 12p deletion was in 1975 by Magnelli and Therman.…”

“…In the literature, at least twelve patients with interstitial deletion on the region of 12p have been reported till date [Stumm et al, 2007;MacDonald et al, 2010]. These patients' clinical phenotype are summarized in Table I.…”

“…Prenatal testing is technically feasible but it is not possible to reliably predict the phenotype from a laboratory finding of interstitial 12p deletion because these abnormalities are often individual cases [Stumm et al, 2007]. Although Magnelli and Therman [1975] proposed a ''12p deletion syndrome'', identical or comparable well characterized cases in the literature are rare [Stumm et al, 2007]. Although, the severity of the anomalies seen in these cases does not appear to correlate with the size of the deletion, it has been suggested that the variation in the clinical features seen in patients with del(12p) may be explained by the different sizes and locations in 12p of the deleted segments [Kivlin et al, 1985].…”

“…There has been a prenatal report on an interstitial deletion (12)(p11.21p13.2), determined by molecular cytogenetic analysis of chorionic villi material which came to attention because of ultrasonic abnormalities like nuchal translucency, temporarily enlarged cisterna magna, peculiar face with marked microretrognathia, and atricular ventricle septum defect (AVSD) [Stumm et al, 2007]. Prenatal testing is technically feasible but it is not possible to reliably predict the phenotype from a laboratory finding of interstitial 12p deletion because these abnormalities are often individual cases [Stumm et al, 2007]. Although Magnelli and Therman [1975] proposed a ''12p deletion syndrome'', identical or comparable well characterized cases in the literature are rare [Stumm et al, 2007].…”

Transcriptional Dysregulation of Neocortical Circuit Assembly in ASD

“…Many of these patients suffer from speech and language delays, moderate to severe intellectual disability, and behavioral deficits that include autistic-like features and stereotypies (Lamb et al, 2012; Rosenfeld et al, 2010; Schanze et al, 2013; Talkowski et al, 2012). Furthermore, several cases of larger deletions that span beyond the entire SOX5 gene have also been reported (Gläser et al, 2003; Lu et al, 2009; Nagai et al, 1995; Stumm et al, 2007). In addition to CNVs, SOX5 interruption by chromosomal rearrangement has been reported in ASD (Talkowski et al, 2012).…”