XLMR genes: update 2000

n/

Measurement of the branching fraction ratios and CP asymmetries in B-→ D0 CP K-decays

We present a preliminary study of $B^- \to D^0_{CP} \pi^-$ and $B^- \to D^0_{CP} K^-$ decays, with the $D^0_{CP}$ reconstructed in the CP-odd eigenstates $K_s \pi^0$, $K_s \omega$, in the CP-even eigenstates $K^+ K^-$, $\pi^+ \pi^-$, and in the (non-CP) flavor eigenstate $K^\mp \pi^\pm$. Using a sample of about 382 million Y(4S) decays into BBbar pairs, collected with the BABAR detector operating at the PEP-II asymmetric-energy B Factory at SLAC, we measure the ratios of the branching fractions R_CP+- and the direct CP asymmetries A_CP+-. The results are: R_CP- = 0.81 \pm 0.10 (stat) \pm 0.05 (syst) R_CP+ = 1.07 \pm 0.10 (stat) \pm 0.04 (syst) A_CP- = -0.19 \pm 0.12 (stat) \pm 0.02 (syst) A_CP+ = 0.35 \pm 0.09 (stat) \pm 0.05 (syst

ANALYSIS OF THE TGFBR1 GENE AS A CANDIDATE GENE IN MARFAN SYNDROME AND RELATED DISORDERS PATIENTS, NEGATIVE FOR FBN1 AND TGFBR2 MUTATIONS

Background Marfan Syndrome (MFS) and related disorders involves particularly skeletal,\ud ocular and cardiovascular. Aortic aneurysms and dissections is the commonest feature of MFS leading to death. MFS caused by mutation in FBN1, and recently, also in TGFBR2 and TGFBR1. Mutation analysis in TGFBR1 gene is needed to know if the mutation is present in patient with MFS and related disorders. Methods One hundred and ninety four patients with MFS and related disorders, who have at least one major criteria of MFS and found to be negative for FBN1 and TGFBR2 mutation, are included. The DNA of the patients were then analyzed for TGFBR1 mutation by direct sequencing of the whole gene. The potency of pathogenicity of the mutation was predicted by referring to previous publication, amino acid changes, multiple alignment analysis and with the help of internetbased software, PolyPhen and SIFT. Results Ten patients were found to carry TGFBR1 missense mutation. Each of them carried a different mutation, except 2 patients carried the same mutation. Seven out of nine of the mutations are considered pathogenic and 2 are not pathogenic. Aortic aneurysm is present in most patients with the mutation. None of the patient with classic MFS has mutation in TGFBR1 gene. Conclusion Despite of mutation analysis on FBN1 and TGFBR2, mutation analysis on TGFBR1 in patient with MFS and related disorders is needed, especially on those who have aortic aneurysm. Knowledge of the presence of a mutation in an individual or in a family, may give a better guidance for comprehensive treatment including genetic counselin

A Case Report of Wolf-Hirschhorn Syndrome (WHS) The Importance of a MLPA test confirmation

A boy, 17 years old, was cytogenetically investigated because of a moderate mental retardation, short stature, hypotonia and several dysmorphisms including microcephaly, a Greek helmet appearance, telecanthus, strabismus, a broad base of the nose with a pointed nasal tip, a wide mouth, thick lips, micrognathia, unusual palmar creases and flat feet. He is the only child of healthy, non-consanguineous Javanese parents from Indonesia. This case was found in the course of our screening program at a special school. In the initial cytogenetic analysis using a GTG-banding technique, a terminal deletion of the short arm of one of his chromosomes 4 was seen, revealing the following karyotype:46,XY,del(4)(p16). Subsequently, Multiplex Ligation-dependent Probe Amplification (MLPA)using subtelomeric probe sets (p070 and p036D; MRC-Holland) demonstrated a deletion of chromosome 4pter and a duplication of 8pter. Fluorescence in-situ hybridization (FISH) using probes for the subtelomeric regions of chromosome 4p and 8p (Vysis) confirmed this finding, showing only one signal for 4pter and 3 signals for 8pter (of which one on the aberrant chromosome 4p). Therefore, the aberration should be designated as:46,XY,der(4)t(4:8)(p16;p23)dn. It appeared to be a de novo unbalanced translocation since both parents showed normal karyotypes. More detailed MLPA analysis using a specific probe set for several MR syndromes (p096; MRC-Holland) showed a deletion of the whole Wolf-Hischhorn Syndrome Critical Region (WHSCR). Further characterization of the deleted and duplicated regions using SNP array analysis is currently in progress. To the best of our knowledge this is the first reported Wolf-Hirschhorn Syndrome patient, confirmed by cytogenetic and molecular analysis in Indonesia. Keywords: Wolf-Hirschhorn Syndrome (WHS), der(4)t(4:8), Multiplex Ligation-dependent Probe Amplification (MLPA

Molecular analyses in Indonesian individuals with intellectual disability and microcephaly

Background Intellectual disability (ID) often coincides with an abnormal head circumference (HC). Since the HC is a reflection of brain size, abnormalities in HC may be a sign of a brain anomaly. Although microcephaly is often secondary to ID, hereditary (autosomal recessive) forms of primary microcephaly (MCPH) exist that result in ID. Objective To investigate mutations in MCPH genes in patients with ID and microcephaly. Methods From a population of 527 Indonesian individuals with ID, 48 patients with microcephaly (9.1 %) were selected. These patients were previously found to be normal upon conventional karyotyping, fragile X mental retardation 1 (FMRl) gene analysis, subtelomeric deletion, and duplication multiplex ligationdependent probe amplification (MLPA). Sanger sequencing for abnormal spindle-like microcephaly-associated (ASPM) and WD repeat domain 62 (WDR62) was performed in all 48 subjects, while sequencing for microcephalin (MCPHl), cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 2 (CD5KRAP2) , centromere protein} (CENPJ), and SCUfALl interrupting locus (STIL) was conducted in only the subjects with an orbitofrontal cortex (OFC) below -4 SD. Results In all genes investigated, 66 single nucleotide polymorphisms (SNPs) and 15 unclassified variants which were predicted as unlikely to be pathogenic (lN2), were identified. Possible pathogenic variants (lN3) were identified in ASPM. However, since none of the patients harboured compound heterozygous likely pathogenic mutations, no molecular MCPH diagnosis could be established. Interestingly, one of the patients harboured the same variants as her unaffected monozygotic twin sister, indicating that our cohort included a discordant twin. Conclusions This study is the first to investigate for possible genetic causes ofMCPH in the Indonesian population. The absence of causative pathogenic mutations in the MCPH genes tested may originate from several factors. The identification of UV2 and UV3 variants as well as the absence of causative pathogenic mutations calls for further investigations

Recurrent Deletion of ZNF630 at Xp11.23 Is Not Associated With Mental Retardation

ZNF630 is a member of the primate-specific Xp11 zinc finger gene cluster that consists of six closely related genes, of which ZNF41, ZNF81, and ZNF674 have been shown to be involved in mental retardation. This suggests that mutations of ZNF630 might influence cognitive function. Here, we detected 12 ZNF630 deletions in a total of 1,562 male patients with mental retardation from Brazil, USA, Australia, and Europe. The breakpoints were analyzed in 10 families, and in all cases they were located within two segmental duplications that share more than 99% sequence identity, indicating that the deletions resulted from non-allelic homologous recombination. In 2,121 healthy male controls, 10 ZNF630 deletions were identified. In total, there was a 1.6-fold higher frequency of this deletion in males with mental retardation as compared to controls, but this increase was not statistically significant (P-value = 0.174). Conversely, a 1.9-fold lower frequency of ZNF630 duplications was observed in patients, which was not significant either (P-value = 0.163). These data do not show that ZNF630 deletions or duplications are associated with mental retardation. (C) 2010 Wiley-Liss, Inc.status: publishe