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Silver-Russell syndrome (SRS) is a clinically heterogeneous disorder characterised mainly by intrauterine and postnatal growth retardation. While maternal uniparental disomy of chromosome 7 is found in 5-10% of SRS patients, recently genetic and epigenetic mutations affecting the imprinting centres on chromosome 11p15 have been reported in up to 64% of patients. Chromosome 11p15 abnormalities reported in SRS include methylation defects in the imprinting centre 1 (ICR1) and maternally inherited duplications involving all or part of the imprinted region of 11p15. Here we report the first published case of SRS with mosaic maternal uniparental disomy of chromosome 11. [ABSTRACT FROM AUTHOR]

Candidate genes and marker loci for cleft lip/palate (CL/P) were tested using linkage analyses and association studies. Eight British families with apparent autosomal dominant inheritance of non-syndromic CL/P participated in the linkage analyses while the association analyses involved 61 unrelated British white people with CL/P and 60 controls. The report of an association between RARA (17q21) and unrelated Australian persons with CL/P (p = 0.016) was not confirmed in British CL/P persons (chi 2 = 0.954, p > 0.1). There was also no evidence of linkage between RARA and the eight CL/P families (Z = -3.211, theta = 0.001). Linkage was excluded between familial CL/P and F13A1 (map position 6p24-25) with an observed maximum lod score of Z = -2.052 at theta = 0.05. No association was found between alleles at VIM (10p13) and the British CL/P subjects (chi 2 = 0.110, p > 0.5). Multipoint analysis excluded linkage between familial CL/P and the markers D1S65 and D1S58 which flank the Van der Woude syndrome locus with a maximum lod score of Z = -4.0. This suggests that the genetic defect underlying VWS is not the same as in non-syndromic CL/P. There was no evidence of linkage between CRTL1 (5q15) and the eight CL/P families (Z = -3.466, theta = 0.05). [ABSTRACT FROM PUBLISHER]

Eight families have been identified with cleft lip, with or without cleft palate (CL/P), inherited in an apparently autosomal dominant manner. Transforming growth factor-alpha (TGFA) has been tested as a candidate gene for clefting in these families. Negative lod scores were generated in an autosomal dominant model with 80% penetrance (Z = -3.152 at theta = 0.05 and Z = -2.49 at theta = 0.05 with only affected subjects scored). After testing with a reduced penetrance of 28%, less negative lod scores were generated (Z = -0.157 at theta = 0.00), but there was still no evidence of linkage. An autosomal recessive model with a penetrance of 35% was also tested. Regardless of the model used there was little evidence of linkage between TGFA and the CL/P phenotype, which is in contrast to the previously published findings of an association between TGFA and CL/P in unrelated subjects. [ABSTRACT FROM PUBLISHER]

A brother and sister are reported with developmental delay and facial features suggestive of the Cornelia de Lange syndrome. Cytogenetic analysis showed them to be trisomic for the region 3q25.1-26.2 because of the inheritance of an unbalanced interchromosomal insertion from their father, who was a balanced insertion carrier. The clinical phenotype and cytogenetic analysis (including chromosome painting studies) in relation to the possible localisation of the Cornelia de Lange gene are discussed. [ABSTRACT FROM PUBLISHER]

We report a mother and daughter with features of the velocardiofacial (VCF) syndrome and monosomy for 22q11 identified using molecular techniques. The mother had surgery as a child for a cleft palate and a congenital heart defect, and her facial features were consistent with the diagnosis. The daughter had developmental delay, absent speech, scoliosis, and similar facial features, but no cleft palate or congenital heart defect. These cases illustrate the considerable intrafamilial variability of the phenotype of VCF syndrome. The clinical and molecular diagnosis of this syndrome is discussed. The phenotypic variability of the VCF syndrome means that many cases may be undiagnosed. [ABSTRACT FROM PUBLISHER]

Three RFLPs at the TGFA locus were studied in 60 unrelated British Caucasian subjects with non-syndromic cleft lip/palate and 60 controls. A highly significant association between the TaqI RFLP and the occurrence of clefting was found (chi 2 = 15.04, p = less than 0.001). No significant association was found with the two other RFLPs studied (BamHI and RsaI). Haplotypes derived from the three RFLPs at the TGFA locus also showed an over-representation of the C2A2B2 haplotype in cases compared to controls. Analyses of genotypes according to type of cleft and the presence or absence of a family history of clefting were also carried out. These results provide further support for the role of TGFA as a gene of major effect in the development of orofacial clefts in humans. [ABSTRACT FROM PUBLISHER]

Presents a letter to the editor of the periodical "Journal of Medical Genetics," concerning mutation in the endothelin B receptor gene in a patient with Shah-Waardenburg syndrome and Down syndrome.

Question: Can a skills training intervention reduce sexual risk behaviours in homeless men who have mental illness? Design: Randomised controlled trial with 6 and 18 months follow up. Setting; 200 bed municipal men's shelter in New York City, New York, USA. Patients: 97 men attending a psychiatric outreach programme. 59 of the men were sexually active at baseline (defined as having had vaginal or oral sex in the past 6 mo); most were >/= 35 years of age (58%), African-American (58%) or Latino (35%), had not completed high school (56% and had psychiatric diagnoses of schizophrenia or schizoaffective disorder (57%) or major or bipolar depression (27%). For sexually active men, follow up was 100% at 6 months and 95% at 18 months. Intervention: 52 men were allocated to the Sex, Games, and Videotapes (SexG) intervention, which involved 15 interactive sessions (2 d/wk for 8 wks) facilitated by a mental health professional and a paraprofessional. Activities included storytelling, competitive games, acting scenes from their daily lives, and practising the decision making skills required for consistent condom use. 45 men were allocated to the control intervention which involved 2 sessions on HIV infection and other sexually transmitted diseases and basic instruction on condom use. Main outcome measures: Main outcome was a sexual risk index (the Vaginal Episode Equivalent [VEE]) based on a semistructured interview given by interviewers blinded to the participant's group assignment. The index assigned scores for each unprotected anal, vaginal, and oral sexual episode. Other outcomes included episodes of sex, episodes with condom use, and high risk episodes (multiple partners and unprotected anal or vaginal sex). Main results: Intention to treat analysis focused on the subgroup of men who were sexually active at baseline (n = 33 in the SexG group and n = 26 in the control group). At 6 months, sexually active men in the SexG group had a lower mean VEE index than sexually active men in the control group (1.0 v 3.1, p = 0.01). Although the total number of episodes of sex were similar for the 2 groups (261 v 247), the SexG group had a higher proportion of episodes with condom use than the control group (73% v 52%, p = 0.04), and a lower proportion of high risk episodes (24% v 58%, p=0.01). The between group difference in mean VEE scores decreased over time from 2.1 at 6 months to 1.6 at 18 months. Among the 38 men who were not sexually active at baseline (n = 19 in each group), the SexG group did not differ from the control group for number who were sexually active (11 v 9) or had unprotected sex (5 v 6) at 18 months. Conclusion: A skills training intervention reduced high risk sexual behaviours in sexually active homeless men who had mental illness. [ABSTRACT FROM AUTHOR]