Clinical, cytogenetic, and molecular characterization of six patients with ring chromosomes 22, including one with concomitant 22q11.2 deletion

Author(s):Show less -

Guilherme, Roberta Santos ^[1] ; Soares, Karina Cunha ^[2] ; Simioni, Milena ^[2] ; Vieira, Tarsis Paiva ^[2] ; Gil-da-Silva-Lopes, Vera Lucia ^[2] ; Kim, Chong Ae ^[3] ; Brunoni, Decio ^[1] ; Spinner, Nancy Bettina ^{[4, 5]} ; Conlin, Laura Kathleen ^{[4, 5]} ; Christofolini, Denise Maria ^[6] ; Kulikowski, Leslie Domenici ^[7] ; Steiner, Carlos Eduardo ^[2] ; Melaragno, Maria Isabel ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Div Genet, Dept Morphol & Genet, BR-04023900 Sao Paulo - Brazil

^[2] Univ Estadual Campinas UNICAMP, Dept Med Genet, Campinas, SP - Brazil

^[3] Univ Sao Paulo, Dept Pediat, Inst Crianca HC FMUSP, Sao Paulo - Brazil

^[4] Univ Penn, Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 - USA

^[5] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 - USA

^[6] ABC, Fac Med, Div Obstet & Gynecol, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Dept Pathol, Lab Citogenom, Sao Paulo - Brazil

• Document type: Journal article
• Source: AMERICAN JOURNAL OF MEDICAL GENETICS PART A; v. 164, n. 7, p. 1659-1665, JUL 2014.
• Web of Science Citations: 9

Abstract

We report here on six patients with a ring chromosome 22 and the range of cytogenetic and phenotypic features presented by them. Genomic analysis was carried out using classical and molecular cytogenetics, MLPA (Multiplex Ligation-dependent Probe Amplification) and genome-wide SNP-array analysis. The ring was found in all patients, but Patient 6 displayed constitutional mosaicism with a normal cell line. Five patients had deletions in the ring chromosome 22, and in four of them the breakpointsunique for each patientcould be identified by genome-wide SNP-array analysis. One patient presented with a 22q11.2 deletion concomitant with the deletion caused by the ring formation. Common phenotypic features included autism, speech delay and seizures, as previously reported for individuals with r(22) and/or 22q13.3 deletions. Investigation of the genes within the deletions revealed multiple genes related to development of the central nervous system, psychomotor delay, severe language impairment, hypotonia, and autistic symptoms. There was no clear correlation between the severity of clinical features and the size of the deleted segment. This study underscores the variability in ring structure and clinical presentation of the r(22) and adds information to the limited literature on this rare disorder. (c) 2014 Wiley Periodicals, Inc. (AU)

• FAPESP's process: 12/51150-0 - Investigation of the mechanisms involved in the formation and stabilization of ring chromosome, supemumerary markers and terminal deletions
• Grantee: Maria Isabel de Souza Aranha Melaragno
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/15572-7 - Investigation of the mechanisms involved in the formation and stabilization of ring chromosome, supernumerary markers and terminal deletion.
• Grantee: Roberta dos Santos Guilherme
• Support Opportunities: Scholarships in Brazil - Doctorate