Interstitial deletion of the long arm of chromosome 5 in a boy with multiple congenital anomalies and mental retardation: Molecular characterization of the deleted region to 5q22.3q23.3

Abstract

Interstitial deletions of the middle portion of the long arm of chromosome 5 are relatively rare. So far, only 36 cases have been reported. Because of the repetitive banding pattern of this region, the extent and localization of the deleted segment has not been well characterized in the majority of reported cases. This has complicated attempts to establish a definite karyotype-phenotype correlation. We report a further case with a de novo interstitial deletion of the region 5q?15 to 5q?22 identified by standard karyotype analysis. The proband presented with failure to thrive, developmental delay, distinct craniofacial dysmorphic features, and associated structural anomalies (amongst them cleft palate, iris colobomata, and horseshoe kidney, which have previously been reported in 5q deletion cases). In addition, this child had an Arnold-Chiari type I malformation that required surgical decompression. FISH studies using BAC clones spanning the 5q15 to 5q22 region revealed that these were all present in both homologues. Use of more distal clones allowed delineation of the deleted region to 5q22.3q23.3 and to narrow down the breakpoints to approximately 200 kb. The 14 Mb deleted region contains about 60 genes but, with the possible exception of FBN2 and DMXL1, there are no obvious candidate genes for the specific components of the phenotype. This case illustrates the discrepancy between cytogenetic and molecular techniques in trying to delineate 5q interstitial deletions. Molecular studies need to be performed on these patients, to establish genotype-phenotype correlation and to understand the role and influence of genes in this region.

Phenotypic and molecular characterisation of a de novo 5q deletion that includes the APC gene

“…Only 37 cases with interstitial deletions of the middle portion of the long arm of chromosome 5 have been reported (Garcia-Minaur et al 2005). Most reported cases of 5q deletions are de novo aberrations, except for three cases with an inherited deletion (Hockey et al 1989;Cross et al 1992;Hastings et al 2000).…”

“…However, the patient described by Raedle et al (2001) was not affected by schizophrenia or other major psychosis. Garcia-Minaur et al (2005) concluded that there is a general phenotype for proximal deletions that encompasses the q15-q22 region (Lindgren et al 1992). Individuals with distal deletions encompassing the q22-q31 region also share a consistent phenotype (Garcia-Minaur et al 2005;Felding and Kristoffersson 1980;Lindgren et al 1992).…”

“…Garcia-Minaur et al (2005) concluded that there is a general phenotype for proximal deletions that encompasses the q15-q22 region (Lindgren et al 1992). Individuals with distal deletions encompassing the q22-q31 region also share a consistent phenotype (Garcia-Minaur et al 2005;Felding and Kristoffersson 1980;Lindgren et al 1992). A list of the clinical symptoms of the four patients with regard to phenotype (type 5q15-q22 and type 5q22-q31) is presented in Table 2.…”

[P2.14]: Mutation of Semaphorin‐6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology

“…This haplotype is restricted to a 6.8 Mbp region, which encompasses sixteen genes, one of which is SEMA6A. Rare deletions of the 5q23 region, which include the SEMA6A locus, have been found in patients with mental retardation and SZ [114,115,116].…”

Genotype–phenotype correlation of a 5q22.3 deletion associated with craniofacial and limb defects

“…It is difficult to accurately cytogenetically determine the deleted segment and the breakpoints because the banding pattern of the long arm of chromosome 5 is repetitious and it has three G-positive metaphase bands of almost equal size (q14, q21 and q23) (Courtens et al, 1998;Garcia-Miñaur et al, 2005). So far, 40 or more such cases have been reported and only a few cases have been analyzed by molecular cytogenetic methods (Tzschach et al, 2006).…”