Case report Mental retardation with rare fragile site expressed at 2q11 Ajlan Tu Èku Èn a, * , Yavuz Renda b , Meral Topc Ëu b , Timur Tuncali c , Isik Bo Èkesoy a a Ankara University Faculty of Medicine, Department of Human Genetics, Ankara, Turkey b Hacettepe University Medical Faculty, Department of Pediatrics, Neurology Division, Ankara, Turkey c Ankara University Faculty of Medicine, Medical Biology Department, Ankara, Turkey Received 1 September 2000; received in revised form 11 October 2000; accepted 23 October 2000 Abstract Several rare autosomal folate sensitive fragile sites were reported in individuals with mental retardation, neurological abnormalities, and multiple congenital malformations. Only three of them: fra(11)(q22.3), fra(X)(q27.3) and fra(X)(q28), are known to be associated with mental retardation and phenotypic abnormalities. A possible association of the other rare fragile sites with idiopathic mental retardation is still being discussed. Here, a girl who has a fragile site at 2q11 with minor congenital anomalies and mental retardation is presented. This case has recalled the question of idiopathic mental retardation that might be the clinical expression of rare FSFS. Fragility was observed at 2q11 with a frequency of 3% in her cells along with a partial endoreduplication at 2 q11 ! qter. q 2000 Published by Elsevier Science B.V. All rights reserved. Keywords: Autosomes; Rare folate sensitive fragile sites; Chromosome 2; Fra (2)(q11); Mental retardation 1. Introduction The fragile sites (FS) are de®ned as special regions of chromosomes which have tendency to break under certain conditions. They are consistently expressed at the same locations in an individual as chromatid or chromosome gaps/breaks, deletions, acentric fragments, stretching, multibranching or triradial ®gures and inherited to the next generations [1]. More than 100 fragile sites on human chromosomes have been reported to date. They are divided into two major groups regarding the occurrence frequency in populations. Fragile sites expressed in all individuals are called common FS, and the rest are called rare FS. Common and rare FS are both classi®ed according to their induction conditions. Over 80 common FS are known and induced by aphidicolin, 5- bromodeoxyuridine (BrdU) or 5-azacytidine. Twenty-®ve rare FS were de®ned as inducable by distamycin A, BrdU or folate depression. Eighteen folate sensitive FS are induced by thymidylate stress [2]. Although there are several reports on patients with mental retardation (MR) revealing cytogenetically expressed FSFS on chromosomes 2, 8, 9, 10, 19, X, the clinical signi®cance of the FSFS, except for three sites (11q22.3, Xq27.3, Xq28) is still unclear [3±5]. 2. Clinical report An 8-year-old girl was referred to the cytogenetic labora- tory for distinguishing female fragile-X syndrome from minor chromosomal abnormalities. She was born in 1986 after a normal pregnancy and labor. She was the ®rst child of a young and healthy couple who were ®rst degree cousins with two children. Her mother had no history of exposure to known mutagens before or during gestation. There was no case of MR in the family as far as we learned. Her height was 117 cm (10 percentile), weight was 21 kg (25 percentile) and occipitofrontal circumference was 51 cm at the time of admission. She had an unusual facial appear- ance with narrow forehead, large everted right ear, small nostrils, long and silent philtrum, high arched palate, thin upper lip, small mouth and incisive margin irregularity of the teeth (Fig. 1). Skin examination has revealed one 5 £ 6 cm cafe-au-lait spot at the right lower abdominal quadrant and two 1 £ 1 cm depigmented areas on the left scapular region. She expressed mild autistic behaviour with dif®cult eye contact, and poor verbal communication. Her developmental milestones were normal: she started to sit without support at 6 months, to walk at 11 months, to Brain & Development 22 (2000) 498±500 0387-7604/01/$ - see front matter q 2000 Published by Elsevier Science B.V. All rights reserved. PII: S0387-7604(00)00189-3 www.elsevier.com/locate/braindev * Corresponding author. Ankara U È niversitesi, Tip Faku Èltesi, Tibbi Biyo- loji Anabilim Dali, Morfoloji Binasi 06100 Sihhiye, Ankara, Turkõ Âye Tel.: 190-312-3103010, ext 351; fax: 1 90-312-310-6370. E-mail address: ajlantukun@yahoo.com (A. Tu Èku Èn).