Multicolor chromosomal bar coding characterizes a de novo interstitial deletion (5)(q33.3q35.2) in a child with multiple congenital malformations

Abstract

We describe a boy with multiple congenital anomalies including a complex heart defect, club feet, adducted thumbs, and facial dysmorphic features. He died at the age of 2 months following cardiac surgery. G-banding analysis identified an abnormal chromosome 5q suspected to be an interstitial deletion (5)(q33q35). Breakpoints of the deleted segment were confirmed as del(5)(q33.3q35) by multicolor fluorescence in situ hybridization (FISH) using two sets of combinatorially labeled band specific YAC clones. Findings are discussed in view of previously published cases.

First report of an interstitial deletion, del(5)(q33.1q35.1) in a girl with primary amenorrhea, seizures, and severe behavioral and developmental deficiencies

“…Of the 10 cases of 5q deletions distal to q33 that have been reported, only one case has similar breakpoints to our proposita's [Gibbons et al, 1999], while the remaining nine cases have various regions of overlap with our patient [Joseph et al, 1990; Kleczkowska et al, 1993; Stratton et al, 1994; Giltay et al, 1997; Gibbons et al, 1999; Krammer et al, 1999; Pauli et al, 1999; Spranger et al, 2000; Schafer et al, 2001; Schiffer et al, 2003]. Although in most of these cases the breakpoints and the extent of the deleted region is not characterized at the molecular level, phenotype–karyotype correlations based on the cytogenetic breakpoints show some very interesting correlations between the extent of the deletion and the phenotype.…”

“…Constitutional interstitial deletions of the long arm of chromosome 5 are extremely rare with only 36 cases reported [Courtens et al, 1998]. Deletions distal to 5q33 have been reported only in 10 patients [Joseph et al, 1990; Kleczkowska et al, 1993; Stratton et al, 1994; Giltay et al, 1997; Gibbons et al, 1999; Krammer et al, 1999; Pauli et al, 1999; Spranger et al, 2000; Schafer et al, 2001; Schiffer et al, 2003]. To our knowledge, there are no reports of constitutional interstitial deletion, del(5)(q33q35) in adolescents.…”

Delineation of a 2.2 Mb microdeletion at 5q35 associated with microcephaly and congenital heart disease

“…When deletions associated with Sotos syndrome (OMIM# 117550) are excluded, only 11 patients with deletions of 5q33.1‐qtel have been described (Fig. 1) [Joseph et al, 1990; Kleczkowska et al, 1993; Stratton et al, 1994; Giltay et al, 1997; Gibbons et al, 1999; Pauli et al, 1999; Spranger et al, 2000; Schafer et al, 2001; Rauch et al, 2003; Schiffer et al, 2003]. In ten of these cases the deletions were large enough to be detected by conventional chromosome analyses and the deletion breakpoints were not estimated precisely.…”

Chromosome 5q subtelomeric deletion syndrome

“…This heart phenotype is apparently related to the NKX2.5 gene, which maps to 5q35.1, and mutations of which were shown in patients with nonsyndromic ASD and AV conduction defects, as well as in patients with idiopathic AV block or tetralogy of Fallot [Schott et al, 1998;Benson et al, 1999]. Microcephaly appears also to be related to 5q35.1-2 [Gibbons et al, 1999;Schafer et al, 2001;Schiffer et al, 2003;BaekvadHansen et al, 2006]. As three of the known microcephaly genes have a presumed function in cell cycle, NPM1, which plays a role in cell-cycle regulation via control of centrosome duplication is an attractive candidate gene for microcephaly related to deletions of 5q35.1 [Baekvad-Hansen et al, 2006].…”

“…From patients with interstitial deletions involving 5q35 [Gibbons et al, 1999;Pauli et al, 1999;Schafer et al, 2001;Schiffer et al, 2003;BaekvadHansen et al, 2006], it is evident that involvement of 5q35.1 is related to significant congenital heart disease, such as Ebstein anomaly, double-outlet-right ventricle, ASD, VSD, cardiomyopathy and AV conduction defects. This heart phenotype is apparently related to the NKX2.5 gene, which maps to 5q35.1, and mutations of which were shown in patients with nonsyndromic ASD and AV conduction defects, as well as in patients with idiopathic AV block or tetralogy of Fallot [Schott et al, 1998;Benson et al, 1999].…”