Fraternal twins with Phelan-McDermid syndrome not involving the SHANK3 gene: case report and literature review
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CASE REPORT
Open Access
Fraternal twins with Phelan-McDermid syndrome not involving the SHANK3 gene: case report and literature review Shan Li1, Ke-wang Xi1, Ting Liu1, Ying Zhang2, Meng Zhang3, Li-dong Zeng3 and Juan Li2*
Abstract Background: Phelan-McDermid syndrome (PMS, OMIM#606232), or 22q13 deletion syndrome, is a rare genetic disorder caused by deletion of the distal long arm of chromosome 22 with a variety of clinical features that display considerably heterogeneous degrees of severity. The SHANK3 gene is understood to be the critical gene for the neurological features of this syndrome. Case presentation: We describe one pair of boy-girl twins with a 22q13 deletion not involving the SHANK3 gene. Interestingly, the clinical and molecular findings of the two patients were identical, likely resulting from germline mosaicism in a parent. The boy-girl twins showed intellectual disability, speech absence, facial dysmorphism, cyanosis, large fleshy hands and feet, dysplastic fingernails and abnormal behaviors, and third-generation sequencing showed an identical de novo interstitial deletion of 6.0 Mb in the 22q13.31-q13.33 region. Conclusions: Our case suggests that prenatal diagnosis is essential for normal parents with affected children due to the theoretical possibility of parental germline mosaicism. Our results also indicated that other genes located in the 22q13 region may have a role in explaining symptoms in individuals with PMS. In particular, we propose that four candidate genes, CELSR1, ATXN10, FBLN1 and WNT7B, may also be involved in the etiology of the clinical features of PMS. However, more studies of smaller interstitial deletions with 22q13 are needed to corroborate our hypothesis and better define the genotype-phenotype correlation. Our findings contribute to a more comprehensive understanding of PMS. Keywords: Phelan-McDermid syndrome, SHANK3, 22q13 interstitial deletion, Neurodevelopmental disorders
Background Phelan-McDermid syndrome (PMS, OMIM#606232), also referred to as 22q13 deletion syndrome, is a rare genetic disorder caused by deletion of the distal long arm of chromosome 22 with a variety of clinical features that display considerably heterogeneous degrees of severity. This syndrome is characterized by global developmental delay, intellectual disability, absent or severely delayed speech, hypotonia, minor dysmorphic features * Correspondence: [email protected] 2 Central Laboratory, The First Hospital of Lanzhou University, Lanzhou, China Full list of author information is available at the end of the article
and autism spectrum disorder (ASD) [1]. The SHANK3 gene has been identified as the critical candidate gene for the neurological features of this syndrome [2]. However, previous genotype-phenotype studies of PMS [3–7] and several case reports of 22q13 interstitial deletion [8– 10] have implied the role of additional genes or regulatory regions proximal to the SHANK3 gene in PMS. Here, we report identical clinical and molecular findings from one pair of boy-girl twins with a de novo
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