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Microdeletion Syndromes
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
Gopalrao V. N. Velagaleti, Nancy J. Carpenter
Recent studies have shown that even in those WHS patients with apparently normal chromosomes, a microdeletion involving the chromosome 4p16.3 region can be demonstrated by molecular techniques including FISH (144). The WHS critical region has been narrowed to a region of 165 kb in 4p16.3 by overlapping deletion analysis (145). Two candidate genes named WHSC1 (Wolf–Hirschhorn syndrome candidate 1) (146) and WHSC2 (Wolf–Hirschhorn syndrome candidate 2) (147) were identified within this region, though no mutations have been identified in either of the genes as yet. A third gene in the region, LETM1 (leucine zipper/EF-hand-containing transmembrane), was considered as an excellent candidate gene for WHS, in particular for seizures (148). However, recent evidence suggests that some of the patients with distinctive WHS phenotype have deletions that are outside the proposed WHS critical region (149) and may be a new critical region for WHS termed WHSCR-2, which lies within a 300–600 kb interval in 4p16.3. There is no consensus on whether the size of the deletion is correlated with the severity of the phenotype (150).
Congenital cavitary optic disc anomaly and Axenfeld’s anomaly in Wolf-Hirschhorn syndrome: A case report and review of the literature
Published in Ophthalmic Genetics, 2018
Mohsin H. Ali, Nathalie F. Azar, Vinay Aakalu, Felix Y. Chau, Javaneh Abbasian, Pete Setabutr, Irene H. Maumenee
Microarray analysis using a comparative genomic hybridization and single nucleotide polymorphism (SNP) array revealed an unbalanced translocation between 4p16.3–15.3 (involving the deletion of 20.55 Mb and 387 genes) and Xp22.33-p22.2 (involving the duplication of 16.07 Mb and 186 genes). Several important deleted genes that are hypothesized to be integral to the pathogenesis of Wolf-Hirschhorn syndrome were involved, including WHSC1, NELFA (WHSC2), and LETM1(2). Chromosomal loci that have reported associations with Axenfeld-Rieger syndrome or related anterior segment dysgenesis phenotypes were not affected. The constellation of clinical findings and the genetic analysis confirmed the diagnosis of Wolf-Hirschhorn syndrome.