A 10.7 Mb interstitial deletion of 13q21 without phenotypic effect defines a further non‐pathogenic euchromatic variant

Abstract

Chromosome 13 deletions are associated with widely varying phenotypes but the clinical picture nearly almost includes mental and growth retardation, craniofacial dysmorphisms, and/or malformations. Several attempts have been made to link monosomy 13q intervals with specific clinical features, but a genotype-phenotype correlation could not be delineated. We report on a woman with a normal phenotype and intelligence referred for chromosomal analysis because of recurrent abortions followed by reproductive loss. Conventional karyotyping revealed an interstitial deletion of chromosome 13q21. By SNP array analysis and FISH the deletion was shown to comprise nearly 10.7 Mb of euchromatic material. This region harbors several genes but an association with recurrent miscarriages has not yet been reported. This is the second report of a 13q21 deletion without psychomotoric retardation, dysmorphisms and malformations. Both cases indicate that this 13q21 deletion can be added to the growing list of euchromatic imbalances without obvious phenotypic abnormalities.

Incomplete penetrance, variable expressivity, or dosage insensitivity in four families with directly transmitted unbalanced chromosome abnormalities

“…This interstitial duplication lies within an extensive 38 Mb region that has a low gene density of 3.1 genes/Mb (Daniel et al, ) and contains at least six examples of directly transmitted UBCAs (Couturier, Morichon‐Delvallez, & Dutrillaux, ; Daniel et al, ; Filges et al, ; Liehr et al, ; López‐Expósito et al, ; Mathijssen et al, ). Four of these have been mapped using molecular cytogenetic methods (Figure b) including three duplications (Daniel et al, ; López‐Expósito et al, ; Mathijssen et al, ) and a deletion with no relevant phenotype (Filges et al, ) to which another deletion in an unaffected individual can be added (Roos et al, ) (Figure a). Of the three overlapping duplications, the first was a 10.6 Mb duplication ascertained in a boy with autistic spectrum disorder and found in his unaffected mother and grandfather (Daniel et al, ); the second was an ∼12 Mb triplication ascertained in an affected boy and duplicated in his two brothers, father, and grandfather who, on closer retrospective examination, had a mild phenotype including some facial dysmorphism, delayed tooth eruption, and adult onset hearing loss (López‐Expósito et al, ); the third was a much larger 21.1 Mb duplication in six members of a three generation pedigree associated with a mild phenotype (Mathijssen et al, ) that overlaps with that in in the duplicated family members of López‐Expósito et al ().…”

Ethical challenges in genotype-driven research recruitment: Box 1.

“…Genomic deletions of this magnitude had been reported in patients with schizophrenia (Need et al 2009); however, they had not been observed in neuropsychiatrically normal subjects and had seldom been seen in the general population (Hansson et al 2007;Roos et al 2008;Itsara et al 2009). Collectively, these findings suggested that such deletions may confer a sizeable risk for neuropsychiatric disease, but additional research was needed to confirm their phenotypic consequences.…”