title: Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family.
abstract: The 16p11.2 deletion is a recurrent genomic event and a significant risk factor for autism spectrum disorders (ASD). This genomic disorder also exhibits extensive phenotypic variability and diverse clinical phenotypes. The full extent of phenotypic heterogeneity associated with the 16p11.2 deletion disorder and the factors that modify the clinical phenotypes are currently unknown. Multiplex families with deletion offer unique opportunities for exploring the degree of heterogeneity and implicating modifiers. Here we reported the clinical and genomic characteristics of three 16p11.2 deletion carriers in a Chinese family. The father carries a de novo 16p11.2 deletion, and it was transmitted to the proband and sib. The proband presented with ASD, intellectual disability, learning difficulty, congenital malformations such as atrial septal defect, scoliosis. His dysmorphic features included myopia and strabismus, flat and broad nasal bridge, etc. While the father shared same neurodevelopmental problems as the proband, the younger brother did not show many of the proband's phenotypes. The possible unmasked mutation of TBX6 and MVP gene in this deleted region and the differential distribution of other genomic CNVs were explored to explain the phenotypic heterogeneity in these carriers. This report demonstrated the different developmental trajectory and discordant phenotypes among family members with the same 16p11.2 deletion, thus further illustrated the phenotypic complexity and heterogeneity of the 16p11.2 deletion.
authors.affiliation: Department of Laboratory Medicine, Children's Hospital Boston, Boston, Massachusetts, USA.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Chen
authors.forename: Liwen
authors.initials: L
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Guo
authors.forename: Jianliang
authors.initials: J
authors.lastname: Shen
authors.forename: Yu
authors.initials: Y
authors.lastname: An
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhu
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhu
authors.forename: Ruolei
authors.initials: R
authors.lastname: Xin
authors.forename: Yihua
authors.initials: Y
authors.lastname: Bao
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Bai-Lin
authors.initials: BL
authors.lastname: Wu
mesh_terms: D044466:Asian People / Q000235:genetics*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002681:China; D002885:Chromosomes, Human, Pair 16; D005190:Family; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D010641:Phenotype; D012307:Risk Factors; D017384:Sequence Deletion