8p23.1 duplication syndrome; common, confirmed, and novel features in six further patients

作者：Barber John C K^*; Rosenfeld Jill A; Foulds Nicola; Laird Sophie; Bateman Mark S; Thomas N Simon; Baker Samantha; Maloney Viv K; Anilkumar Arayamparambil; Smith Wendy E; Banks Valerie; Ellingwood Sara; Kharbutli Yara; Mehta Lakshmi; Eddleman Keith A; Marble Michael; Zambrano Regina; Crolla John A; Lamb Allen N

来源：American Journal of Medical Genetics, Part A, 2013, 161A(3): 487-500.

DOI：10.1002/ajmg.a.35767

• chromosomes
• human
• pair 8
• chromosome duplication
• 8p23.1
• genomic disorder
• common features
• candidate genes
• variable penetrance
• DNA array

The 8p23.1 duplication syndrome is a relatively rare genomic condition that has been confirmed with molecular cytogenetic methods in only 11 probands and five family members. Here, we describe another prenatal and five postnatal patients with de novo 8p23.1 duplications analyzed with oligonucleotide array comparative genomic hybridization (oaCGH). Of the common features, mild or moderate developmental delays and/or learning difficulties have been found in 11/12 postnatal probands, a variable degree of mild dysmorphism in 8/12 and congenital heart disease (CHD) in 4/5 prenatal and 3/12 postnatal probands. Behavioral problems, cleft lip and/or palate, macrocephaly, and seizures were confirmed as additional features among the new patients, and novel features included neonatal respiratory distress, attention deficit hyperactivity disorder (ADHD), ocular anomalies, balance problems, hypotonia, and hydrocele. The core duplication of 3.68Mb contains 31 genes and microRNAs of which only GATA4, TNKS, SOX7, and XKR6 are likely to be dosage sensitive genes and MIR124-1 and MIR598 have been implicated in neurocognitive phenotypes. A combination of the duplication of GATA4, SOX7, and related genes may account for the variable penetrance of CHD. Two of the duplications were maternal and intrachromosomal in origin with maternal heterozygosity for the common inversion between the repeats in 8p23.1. These additional patients and the absence of the 8p23.1 duplications in published controls, indicate that the 8p23.1 duplication syndrome may now be considered a pathogenic copy number variation (pCNV) with an estimated population prevalence of 1 in 58,000.

• 出版日期2013-3