A New Inherited Interstitial Deletion of the Distal Long Arm of Chromosome 4,

Deletion of the terminal part of long arm of chromosome 4 is a condition characterized by facial dysmorphisms, cardiac and limb defects, and developmental delay. Deletions usually involve the terminal part of the chromosome and most frequently are interstitial. Here, we report a de novo interstitial deletion resulting in a microdeletion of 6.9 Mb involving 4q31.3-q32.1 segment, detected by SNPs-Array technique in a 4-year-old female showing severe speech delay, mild facial dysmorphisms, and joint laxity. Phenotype-genotype relationships looking at the genes involved in this part of the chromosome were also carried out and data compared with those previously described.

Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

De novo 6.9 Mb interstitial deletion on chromosome 4q31.1‐q32.1 in a girl with severe speech delay and dysmorphic features

Fabretto¹,

Rocca²,

Perrone³

et al. 2012

“…Distal deletions commonly encompass 4q31-34, whereas the less common proximal deletions involve 4q11-q31 [Aladhami et al, 2000].…”

Section: Introductionmentioning

confidence: 99%

4q12–4q21.21 deletion genotype–phenotype correlation and the absence of piebaldism in presence of KIT haploinsufficiency

Hemati

Souich

Boerkoel

2014

Chromosome 4q deletion syndrome is a rare intellectual disability disorder caused by a variety of non-recurrent deletions of 4q. We describe the evolution of the phenotypic features of a female patient with a previously unreported deletion of 4q12-4q21.21 (hg 18; 54,711,575-79,601,919). By review reported individuals with interstitial deletions extending telomeric from 4q12 have syndromic intellectual disability with variable piebaldism. We expand the phenotype to include dolichocephaly, pectus excavatum, hip dysplasia, pes planus, myopia, lens opacities, and an absence of spoken language but not of communication through sign. The proposita also did not have piebaldism suggesting again that piebaldism arises from a mechanism more complex than simple haploinsufficiency of KIT. Comparing deletions among affected individuals localizes the critical interval within 4q12-4q13.1, although the absence of molecular boundaries for nearly all reported cases precludes precise delineation and genotype-phenotype correlation.

“…Interstitial deletions of chromosome band 4q32 are rare, and only five patients have been reported to date [Sarda et al, 1992; Aladhami et al, 2000; Keeling et al, 2001; Ramanathan et al, 2004]. Clinical problems of these patients comprised mental retardation, obesity, and facial dysmorphic signs, but the small number of well‐characterized patients has so far precluded genotype–phenotype correlations or the delineation of a “4q32 deletion syndrome.”…”

Section: Introductionmentioning

confidence: 99%

Characterization of an interstitial 4q32 deletion in a patient with mental retardation and a complex chromosome rearrangement

Tzschach

Menzel

Erdogan

et al. 2010

Interstitial deletions of chromosome band 4q32 are rare. We report on a 22-year-old female patient with a de novo interstitial deletion of chromosome 4q32 and a balanced translocation t(2;5)(p21;q12.1). Clinical problems of the patient comprised mild to moderate mental retardation, psychosis, obesity, broad nasal root, sparse lateral eyebrows, thin upper lip, short philtrum, micrognathia, and strabismus. Analysis by whole genome array CGH using an Agilent 244K oligonucleotide array and subsequent FISH using BAC clones from the 4q32 region revealed an unexpectedly complex rearrangement comprising a deletion of approximately 10 Mb in 4q32.1q32.3 and the insertion of two small fragments of 0.8 and 0.11 Mb originating from the derivative chromosome 4q32 into derivative chromosome 5q. The breakpoints of the t(2;5) translocation were mapped by BAC-FISH; no genes were disrupted by these breakpoints. The deleted interval in 4q32 harbored more than 30 genes, and haploinsufficiency of one or several of these genes is likely to have caused the clinical problems of the patient. Candidate genes for cognitive defects are GRIA2, GLRB, NPY1R, and NPY5R. In conclusion, this patient increases our knowledge about the phenotypic consequences of interstitial 4q32 deletions. Reports of patients with overlapping deletions will be needed to elucidate the role of individual genes and to establish genotype-phenotype correlations.