Refinement of genotype‐phenotype correlation in 18 patients carrying a 1q24q25 deletion. (25th February 2015)

• Record Type: Journal Article
• Authors: Chatron, Nicolas; Haddad, Véronique; Andrieux, Joris; Désir, Julie; Boute, Odile; Dieux, Anne; Baumann, Clarisse; Drunat, Séverine; Gérard, Marion; Bonnet, Céline; Leheup, Bruno; Till, Marianne; Rossi, Massimiliano; Flori, Elisabeth; Alembik, Yves; Stewart, Helen; McParland, Joanna; Bernardini, Laura; Castelluccio, Pia; Roos, Laura; Tümer, Zeynep; Fagan, Kerry; Hackett, Anna; Bain, Nicole; van Haeringen, Arie; Ruivenkamp, Claudia; Benzacken, Brigitte; Sanlaville, Damien; Edery, Patrick; Aboura, Azzedine; Schluth‐Bolard, Caroline;
• Is Part Of: American journal of medical genetics. Volume 167:Number 5(2015:May)
• Page Start: 1008
• Page End: 1017
• Publication Date: 2015-02-25
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36856
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga36856-sec-0001" sec-type="section"> <p>Interstitial deletion 1q24q25 is a rare rearrangement associated with intellectual disability, growth retardation, abnormal extremities and facial dysmorphism. In this study, we describe the largest series reported to date, including 18 patients (4M/14F) aged from 2 days to 67 years and comprising two familial cases. The patients presented with a characteristic phenotype including mild to moderate intellectual disability (100%), intrauterine (92%) and postnatal (94%) growth retardation, microcephaly (77%), short hands and feet (83%), brachydactyly (70%), fifth finger clinodactyly (78%) and facial dysmorphism with a bulbous nose (72%), abnormal ears (67%) and micrognathia (56%). Other findings were abnormal palate (50%), single transverse palmar crease (53%), renal (38%), cardiac (38%), and genital (23%) malformations. The deletions were characterized by chromosome microarray. They were of different sizes (490 kb to 20.95 Mb) localized within chromosome bands 1q23.3–q31.2 (chr1:160797550–192912120, hg19). The 490 kb deletion is the smallest deletion reported to date associated with this phenotype. We delineated three regions that may contribute to the phenotype: a proximal one (chr1:164, 501, 003–167, 022, 133), associated with cardiac and renal anomalies, a distal one (chr1:178, 514, 910–181, 269, 712) and an intermediate 490 kb region (chr1:171970575–172460683, hg19), deleted in the most of the patients, and containing DNM3, MIR3120 and MIR214 that may play an important role in the phenotype. However, this genetic region seems complex with multiple regions giving rise to the same phenotype. © 2015 Wiley Periodicals, Inc.</p> </sec> </abstract>