Dataset Information

De novo unbalanced translocation (4p duplication/8p deletion) in a patient with autism, OCD, and overgrowth syndrome.

ABSTRACT: Chromosomal abnormalities, such as unbalanced translocations and copy number variants (CNVs), are found in autism spectrum disorders (ASDs) [Sanders et al. (2011) Neuron 70: 863-885]. Many chromosomal abnormalities, including sub microscopic genomic deletions and duplications, are missed by G-banded karyotyping or Fragile X screening alone and are picked up by chromosomal microarrays [Shen et al. (2010) Pediatrics 125: e727-735]. Translocations involving chromosomes 4 and 8 are possibly the second most frequent translocation in humans and are often undetected in routine cytogenetics [Giglio et al. (2002) Circulation 102: 432-437]. Deletions of 4p16 have been associated with Wolf-Hirschhorn syndrome while 4p16 duplications have been associated with an overgrowth syndrome and mild to moderate mental retardation [Partington et al. (1997) Journal of Medical Genetics 34: 719-728]. The 8p23.3 region contains the autism candidate gene DLGAP2, which can contribute to autism when disrupted [Marshall et al. (2008) The American Journal of Human Genetics 82: 477-488] . There has been a case report of a family with autism spectrum disorder (ASD), prominent obsessional behavior, and overgrowth in patients with der (8) t (4;8) p (16;23) [Partington et al. (1997)]. This is an independent report of a male patient with autism, obsessive compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), and an overgrowth syndrome, whose de novo unbalanced translocation der (8) t (4;8) p (16.1?ter; 23.1?ter) was initially missed by routine cytogenetics but detected with SNP microarray, allowing higher resolution of translocation breakpoints.

SUBMITTER: Sagar A

PROVIDER: S-EPMC5444998 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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De novo unbalanced translocation (4p duplication/8p deletion) in a patient with autism, OCD, and overgrowth syndrome.

Sagar Angela A Pinto Dalila D Najjar Fedra F Guter Stephen J SJ Macmillan Carol C Cook Edwin H EH

American journal of medical genetics. Part A 20170413 6

Chromosomal abnormalities, such as unbalanced translocations and copy number variants (CNVs), are found in autism spectrum disorders (ASDs) [Sanders et al. (2011) Neuron 70: 863-885]. Many chromosomal abnormalities, including sub microscopic genomic deletions and duplications, are missed by G-banded karyotyping or Fragile X screening alone and are picked up by chromosomal microarrays [Shen et al. (2010) Pediatrics 125: e727-735]. Translocations involving chromosomes 4 and 8 are possibly the seco ...[more]

PMID: 28407363

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Project description:Background1q43-q44 deletion syndrome is a well-defined chromosomal disorder which is characterized by moderate to severe mental retardation, and variable but characteristic facial features determined by the size of the segment and the number of genes involved. However, patients with 1q43-q44 duplication with a clinical phenotype comparable to that of 1q43-q44 deletion are rarely reported. Moreover, pure 1q43-q44 deletions and duplications derived from balanced insertional translocation within the same family with precisely identified breakpoints have not been reported.Case presentationThe proband is a 6-year-old girl with profound developmental delay, mental retardation, microcephaly, epilepsy, agenesis of the corpus callosum and hearing impairment. Her younger brother is a 3-month-old boy with macrocephaly and mild developmental delay in gross motor functions. G-banding analysis of the subjects at the 400-band level did not reveal any subtle structural changes in their karyotypes. However, single-nucleotide polymorphism (SNP) array analysis showed a deletion and a duplication of approximately 6.0 Mb at 1q43-q44 in the proband and her younger brother, respectively. The Levicare analysis pipeline of whole-genome sequencing (WGS) further demonstrated that a segment of 1q43-q44 was inserted at 14q23.1 in the unaffected mother, which indicated that the mother was a carrier of a 46,XX,ins(14;1)(q23.1;q43q44) insertional translocation. Moreover, Sanger sequencing was used to assist the mapping of the breakpoints and the final validation of those breakpoints. The breakpoint on chromosome 1 disrupted the EFCAB2 gene in the first intron, and the breakpoint on chromosome 14 disrupted the PRKCH gene within the 12th intron. In addition, fluorescence in situ hybridization (FISH) further confirmed that the unaffected older sister of the proband carried the same karyotype as the mother.ConclusionHere, we describe a rare family exhibiting pure 1q43-q44 deletion and duplication in two siblings caused by a maternal balanced insertional translocation. Our study demonstrates that WGS with a carefully designed analysis pipeline is a powerful tool for identifying cryptic genomic balanced translocations and mapping the breakpoints at the nucleotide level and could be an effective method for explaining the relationship between karyotype and phenotype.

Dataset Information

De novo unbalanced translocation (4p duplication/8p deletion) in a patient with autism, OCD, and overgrowth syndrome.

Publications

De novo unbalanced translocation (4p duplication/8p deletion) in a patient with autism, OCD, and overgrowth syndrome.

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