Familial 4.8MB deletion on 18q23 associated with growth hormone insufficiency and phenotypic variability

• Published in: American journal of medical genetics. Part A 2012-03, Vol.158A (3), p.611-616
• Main Authors: Margarit, Ester, Morales, Carme, Rodriguez-Revenga, Laia, Monne, Raquel, Badenas, Cèlia, Soler, Anna, Clusellas, Núria, Mademont, Irene, Sanchez, Aurora
• Format: Article
• Language: English
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.34221

The deletion of the long arm of chromosome 18 causes a contiguous gene deletion syndrome with a highly variable phenotype, usually related to the extent of the deleted region. The most commonly reported clinical features include: decreased growth, microcephaly, facial abnormalities, hypotonia, developmental delay, intellectual disability, congenital aural atresia with hearing impairment and limb anomalies. Here we report on a familial terminal deletion of 18q23 region transmitted from a mother to two daughters, resulting in a remarkable phenotypic variability. The deletion was first detected by conventional cytogenetic analysis in one daughter and subsequently characterized using fluorescence in situ hybridization (FISH) and array-CGH. FISH analysis using subtelomeric 18p and 18q probes confirmed the 18qter deletion in the three patients, and FISH with a whole chromosome painting probe specific for chromosome 18 excluded rearrangements with other chromosomes. Array-CGH analysis allowed us to precisely define the extent of the deletion, which spans 4.8Mb from 71,236,891 to 76,093,303 genomic positions and includes GALR1 and MBP genes, among others. High-resolution analysis of the deletion, besides a detailed clinical assessment, has provided important data for phenotype-genotype correlation and genetic counseling in this family. Furthermore, this study adds valuable information for phenotype-genotype correlation in 18q- syndrome and might facilitate future search for candidate genes involved in each phenotypic trait. © 2012 Wiley Periodicals, Inc.