Clinical and Genetic Heterogeneity of the 15q13.3 Microdeletion Syndrome

Molecular Syndromology

Michael Leipoldt¹  Ariane Hassfurther¹  Judith Fischer¹  Eleni Komini¹ 

[1] aInstitute of Human Genetics, University Medical Center Freiburg, Freiburg, Germany

关键词: Copy number variations;    Microdeletion 15q13.3;    Segmental duplications;   

DOI  :  10.1159/000443343

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

The 15q13.3 microdeletion is a recurrent CNV, presumably mediated by NAHR between segmental duplications in chromosome 15. The 15q13.3 deletion and duplication are associated with a wide range of clinical manifestations, such as intellectual deficits, seizures, autism, language and developmental delay, neuropsychiatric impairments, and behavioral problems illustrating incomplete penetrance and expressivity. This study comprises an evaluation of 106 symptomatic patients carrying the heterozygous deletion, as well as of 21 patients carrying the duplication, who have been described in previous studies. The analysis shows considerable heterogeneity for the manifestation of different key symptoms and familiar occurrence. Furthermore, 8 new patients are introduced. Convoluted familiar connections give new insights into the complexity of symptomatic manifestation. In previous studies, different opinions have been expressed as to the nature and precise location of the deletion breakpoints. Here, we show that not CHRNA7 and CHRFAM7A, but rather FAM7A or GOLGA8, serve as breakpoint regions concerning our patients. The deletion is described as heterogeneous in size. However, we assume that not only different breakpoints but also the imprecision of aCGH analysis on chromosome 15 due to segmental duplications accounts for the variability in size.

【 授权许可】

Unknown