The behavior of 60 children with Down syndrome (cDS), aged 4 to 21 years, was assessed by parent and teacher report using the Reiss psychopathology rating scale for dual diagnosis (mental disability plus mental illness). Standard forms contained 12 categories of abnormal behavior (e.g., Psychosis ), each with five descriptive items (e.g., bizarre ideas ) that could be scored as no problem, problem, and major problem (0, 1, or 2 points). Total scores for individual cDS (mean of two raters) ranged from 3 to 43 out of a potential 120 points, with a mean of 14.8 points and a standard deviation of 9.5. There were no significant differences by sex, age, or ethnicity. The highest aggregate scores among the 60 cDS were in the psychometric categories of Attention‐Deficit (156 points), Anger/Self Control (154.5), and Psychosis (109) and for component items such as communication problems (55 points) under the Psychosis category; distracted (48.5) or disobedient (42.5) under the Attention‐Deficit category; and temper tantrums (36.5), impulsive (32), or impatient (31.5) under the Anger/Self‐Control category. Agreement between parent and teacher raters was over 75% for 38 of the 60 items and above 60% for an additional 15. Selection of cDS with scores over 10 points yielded 24 families who chose parental guidance and 14 who chose professional referral. The structure of the Reiss instrument was useful for cDS, distinguishing behaviors potentially related to medical problems from true psychopathology. © 2003 Wiley‐Liss, Inc.

Cytogenetic and molecular studies have provided evidence of the clustering of chromosome 2 deletion breakpoints in radiation‐induced murine acute myeloid leukemia (AML). Moreover, clustering occurs in at least two fragile domains rich in telomere‐like arrays. Here we describe a physical map of the distal breakpoint cluster and confirm the presence of inverted head‐to‐head telomeric sequence arrays. These potentially recombinogenic sequences were not, however, the direct focus for post‐irradiation chromosome breakage in AML. Instead, the two arrays bordered a 2.5‐kb sequence with properties expected of a nuclear matrix attachment region (MAR). The putative MAR co‐localized in the fragile domain with genes important to the hemopoietic system (leukocyte tyrosine kinase, zinc finger protein 106, erythrocyte protein band 4.2, and β 2 ‐microglobulin ( β2m )); the β2m subdomain was a particular focus of breakage. On the basis of these and other data, we suggest that AML‐associated chromosome 2 fragility in the mouse is a consequence of domain‐specific fragility in genomic domains containing numerous genes critical to the hemopoietic system. Copyright © Crown Copyright 2002. Recorded with the permission of the controller of Her Majesty's Stationery Office. Published by Wiley‐Liss, Inc.

Radiation-induced acute myeloid leukemias (AMLs) in the mouse are characterized by chromosome 2 deletions. Previous studies showed that a minimal deleted region (mdr) of ∼6.5 cM is lost from one homologue in chromosome 2–deleted AMLs. An AML tumor suppressor gene is proposed to map within this mdr. In this study, we refine the mdr to a 1 cM interval between markers D2Mit126 and D2Mit185 by microsatellite analysis of 21 primary radiation-induced F1 AMLs. The construction of a partial yeast artificial chromosome (YAC) contig spanning the mdr and the location of six known genes indicated that the 1 cM mdr is homologous to human 11p11–12, a region implicated in some human AMLs. Screening of five cell lines derived from primary radiation-induced AMLs for homozygous loss of microsatellites and genes mapping within the mdr revealed loss of both copies of the hemopoietic tissue-specific transcription factor Sfpi1 (PU.1/Spi1) in one cell line. Studies of primary and F1 AMLs failed to implicate Sfpi1 as the AML tumor suppressor gene. YAC contig construction, together with data suggesting that the critical gene flanks Sfpi1, represents significant progress toward identifying an AML tumor suppressor gene. Genes Chromosomes Cancer 24:95–104, 1999. © 1999 Wiley-Liss, Inc.