exudates and Chromosome-Deletion

Azoospermia factor region (AZF) deletions (AZFa, AZFb, AZFc and AZFd) in the Y chromosome were analysed in male infertility subjects in various populations with conflicting results. This study comprised of 54 infertile males and 63 fertile controls, and the frequency of AZFa, AZFb, AZFc and AZFd deletions were determined using conventional polymerase chain reaction (PCR) as well as real-time PCR-high resolution melting analysis-based methods. The results of this study showed that, three of 54 cases (5.55%) had AZF (a, b and c) deletions (two had AZFc and one had AZFa deletions). Four cases were found to have AZFd deletions (7.4%) with two of them being associated with AZFc deletions (P = 0.028). The frequency of AZF (a, b and c) deletions in Malaysian infertile male subjects was found to be comparable with other populations. AZFd deletions were found to be significant (P < 0.05) in male infertility and it may be associated with other types of AZF deletions.

Topics: Adult; Azoospermia; Case-Control Studies; Chromosome Deletion; Chromosomes, Human, Y; Genetic Testing; Genotype; Humans; Infertility, Male; Malaysia; Male; Phenotype; Polymerase Chain Reaction; Risk Factors

Complete deletions in the AZF (a, b, and c) sub-regions of the Y-chromosome have been shown to contribute to unexplained male infertility. However, the role of partial AZFc deletions in male infertility remains to be verified. Three types of partial AZFc deletions have been identified. They are gr/gr, b1/b3, and b2/b3 deletions. A recent meta-analysis showed that ethnic and geographical factors might contribute to the association of partial AZFc deletions with male infertility. This study analyzed the association of partial AZFc deletions in Malaysian infertile males. Fifty two oligozoospermic infertile males and 63 fertile controls were recruited to this study. Screening for partial AZFc deletions was done using the two sequence-tagged sites approach (SY1291 and SY1191) which were analyzed using both the conventional PCR gel-electrophoresis and the high resolution melt, HRM method. Gr/gr deletions were found in 11.53% of the cases and 9.52% of the controls (p = 0.725). A B2/b3 deletion was found in one of the cases (p = 0.269). No B1/b3 deletions were identified in this study. The results of HRM analysis were consistent with those obtained using the conventional PCR gel-electrophoresis method. The HRM analysis was highly repeatable (95% limit of agreement was -0.0879 to 0.0871 for SY1191 melting temperature readings). In conclusion, our study showed that partial AZFc deletions were not associated with male infertility in Malaysian subjects. HRM analysis was a reliable, repeatable, fast, cost-effective, and semi-automated method which can be used for screening of partial AZFc deletions.

Topics: Chromosome Deletion; Chromosomes, Human, Y; Humans; Infertility, Male; Malaysia; Male; Real-Time Polymerase Chain Reaction

We report the first two Malaysian children with partial deletion 9p syndrome, a well delineated but rare clinical entity. Both patients had trigonocephaly, arching eyebrows, anteverted nares, long philtrum, abnormal ear lobules, congenital heart lesions and digital anomalies. In addition, the first patient had underdeveloped female genitalia and anterior anus. The second patient had hypocalcaemia and high arched palate and was initially diagnosed with DiGeorge syndrome. Chromosomal analysis revealed a partial deletion at the short arm of chromosome 9. Karyotyping should be performed in patients with craniostenosis and multiple abnormalities as an early syndromic diagnosis confers prognostic, counselling and management implications.

Topics: Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 9; Female; Genetic Testing; Humans; Infant; Malaysia; Male

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive genetic disorder characterized by rapidly progressive muscle weakness. The disease is caused by deletion, duplication or point mutation of the dystrophin gene, located on the X chromosome (Xp21). Deletion accounts for 60% of the mutations within the 79 exons of the dystrophin gene. Seven exons (43, 44, 45, 46, 49, 50, and 51) were found to be most commonly deleted among the Asian patients. To detect the frequency of deletion of these 7 exons in Malaysian DMD patients, we carried out a molecular genetic analysis in 20 Malaysian DMD patients. The mean age of initial presentation was 60 months (SD 32 months, range 5-120 months). Fourteen patients were found to have deletion of at least one of the seven exons. The remaining six patients did not show any deletion on the tested exons. Deletions of exons 49, 50 and 51 were the most frequent (71.43%) and appear to be the hot spots in our cohort of patients.

Topics: Adolescent; Child; Child, Preschool; Chromosome Deletion; Dystrophin; Exons; Humans; Infant; Malaysia; Male; Muscular Dystrophy, Duchenne

The use of STR multiplexes with the incorporated gender marker Amelogenin is common practice in forensic DNA analysis. However, when a known male sample shows a dropout of the Amelogenin Y-allele, the STR system falsely genotypes it as a female. To date, our laboratory has observed 18 such cases: 12 from our Y-STR database and six from casework. A study on 980 male individuals in the Malaysian population using the AmpFlSTR Y-filer has revealed a distinct Y-chromosome haplotype associated with the Amelogenin nulls. Our results showed that whilst the Amelogenin nulls were noticeably absent among the Chinese, both the Indians and Malays exhibited such mutations at 3.2 and 0.6%, respectively. It was also found that the Amelogenin negative individuals predominantly belonged to the J2e lineage, suggesting the possibility of a common ancestor for at least some of these chromosomes. The null frequencies showed concordance with the data published in Chang et al. [Higher failures of Amelogenin sex test in an Indian population group, J. Forensic Sci. 48 (2003) 1309-1313] on a smaller Malaysian population of 338 males which used a Y-STR triplex. In the current study, apart from the absence of the Amelogenin Y-locus, a complete absence of the DYS458 locus in all the nulls was also observed. This study together with the 2003 study has indicated a similar deletion region exists on the Y(p)11.2 band in all the 18 Y-chromosomes. Using bioinformatics, this deletion has been mapped to a region of at least 1.13 Mb on the Y(p)11.2 encompassing the Amelogenin, MSY1 minisatellite and DYS458 locus. Further, the Y-filer haplotypes revealed an additional null at Y-GATA H4 in two of the Indian males presented here.

Topics: Amelogenin; Asian People; Chromosome Deletion; Chromosomes, Human, Y; DNA Fingerprinting; Genetics, Population; Haplotypes; Humans; Malaysia; Male; Polymerase Chain Reaction; Tandem Repeat Sequences; White People

The survival motor neuron 1 (SMN1) gene has been recognized to be responsible for spinal muscular atrophy (SMA) because it is homozygously deleted in more than 90% of SMA patients, irrespective of their clinical severity, whereas the neuronal apoptosis inhibitory protein (NAIP) gene is now considered to be a modifying factor of the severity of SMA. In Malaysia, it remains to be elucidated whether deletion of the SMN1 gene is also a main cause of SMA or whether deletion of the NAIP gene is found in the SMA patients.. To clarify the pathogenesis of SMA in Malaysia, a deletion analysis of the SMN1 and NAIP genes was performed in 24 Malaysian SMA patients. Deletion analysis of exons 7 and 8 of the SMN1 gene was performed according to the method described by van der Steege et al., while deletion analysis of exon 5 of the NAIP gene was performed according to a method described by Roy et al.. Homozygous deletion of SMN1 exon 7 and exon 8 were identified in 19 out of 24 patients (79%). As to the NAIP gene, deletion of exon 5 was detected in six out of 24 patients (25%). NAIP gene deletion was correlated with severity of the disease.. Deletion of the SMN1 exon 7 is a major cause of SMA in Malaysia, and NAIP gene deletions are not rare in type I SMA in Malaysia. The lower percentage of the SMN1 gene deletion may be due to the possibility that the present study included some patients without SMN1 gene abnormality and/or some patients with non-deletion type mutations in the SMN1 gene.

Topics: Asian People; Child; Child, Preschool; Chromosome Deletion; Cyclic AMP Response Element-Binding Protein; Female; Humans; Infant; Infant, Newborn; Malaysia; Male; Nerve Tissue Proteins; Neuronal Apoptosis-Inhibitory Protein; RNA-Binding Proteins; SMN Complex Proteins; Spinal Muscular Atrophies of Childhood; Survival of Motor Neuron 1 Protein

Amelogenin paralogs on Chromosome X (AMELX) and Y (AMELY) are commonly used sexing markers. Interstitial deletion of Yp involving the AMELY locus has previously been reported. The combined frequency of the AMELY null allele in Singapore and Malaysia populations is 2.7%, 0.6% in Indian and Malay ethnic groups respectively. It is absent among 541 Chinese screened. The null allele in this study belongs to 3 Y haplogroups; J2e1 (85.7%), F* (9.5%) and D* (4.8%). Low and high-resolution STS mapping, followed by sequence analysis of breakpoint junction confirmed a large deletion of 3 to 3.7-Mb located at the Yp11.2 region. Both breakpoints were located in TSPY repeat arrays, suggesting a non-allelic homologous recombination (NAHR) mechanism of deletion. All regional null samples shared identical breakpoint sequences according to their haplogroup affiliation, providing molecular evidence of a common ancestry origin for each haplogroup, and at least 3 independent deletion events recurred in history. The estimated ages based on Y-SNP and STR analysis were approximately 13.5 +/- 3.1 kyears and approximately 0.9 +/- 0.9 kyears for the J2e1 and F* mutations, respectively. A novel polymorphism G > A at Y-GATA-H4 locus in complete linkage disequilibrium with J2e1 null mutations is a more recent event. This work re-emphasizes the need to include other sexing markers for gender determination in certain regional populations. The frequency difference among global populations suggests it constitutes another structural variation locus of human chromosome Y. The breakpoint sequences provide further information to a better understanding of the NAHR mechanism and DNA rearrangements due to higher order genomic architecture.

Topics: Alleles; Amelogenin; Asian People; Base Sequence; Cell Cycle Proteins; Chromosome Deletion; Chromosome Mapping; Chromosomes, Human, Y; DNA; Gene Dosage; Gene Frequency; Genetic Markers; Haplotypes; Humans; Linkage Disequilibrium; Malaysia; Male; Phylogeny; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Recombination, Genetic; Sequence Tagged Sites; Sex Determination Analysis; Singapore

A 3-year-old girl with facial dysmorphic features suggestive of Cornelia de Lange syndrome was seen in the ophthalmology unit for a right leukocoria. The leukocoria was found to be caused by a large retinoblastoma and the right eye was enucleated. Chromosomal analysis revealed partial chromosome 13q deletion involving band 14 which is associated with a high risk of retinoblastoma. This case shows that patient with chromosome 13q deletion syndrome cannot be diagnosed based on dysmorphic features only. Chromosomal analysis is warranted in all infants with facial dysmorphism suggestive of Cornelia de Lange syndrome so that those with chromosome 13q deletion can be referred early for early detection of retinoblastoma.

Topics: Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 13; De Lange Syndrome; Female; Humans; Malaysia

Beta-thalassaemia major is one of the commonest genetic disorders in South East Asia. The strategy for the community control of beta-thalassaemia major requires the characterisation of the spectrum of beta-globin gene mutations in any multi-ethnic population. There is only a single report of mutation analyses of the beta-globin gene in an isolated Kadazandusun community in Kota Belud, Sabah, Malaysia, which showed the presence of a common 45 kb deletion.. To confirm the observation that this large deletion is the commonest beta-globin gene mutation among the Kadazandusun and other indigenous populations in Sabah, Malaysia, we performed polymerase chain reaction (PCR) analysis of the beta-globin gene in ten children with beta-thalassaemia major attending the Thalassaemia Centre, Queen Elizabeth Hospital, the major paediatric referral centre in Kota Kinabalu, Sabah.. The 45 kb deletion was confirmed to be the commonest mutation found in the Kadazandusun, Bajau and Murut populations, whereby it was detected in 19 out of the 20 (95 percent) alleles analysed. The other mutation was due to an IVS-1 position 1 G > T mutation.. This finding confirmed the deletion in the homozygous state was associated with a severe phenotype. The reason for the predominance of this mutation in Kota Kinabalu is most likely to be due to founder effects and possibly intermarriages between the various ethnic groups. Prenatal diagnosis using PCR for this common mutation is feasible in this community. Medical workers and scientists at molecular diagnostic centres serving large South East Asian populations should incorporate a diagnostic strategy for this deletion in the appropriate population. Future studies on these indigenous ethnic groups in other areas and other groups in Sabah are required.

Topics: Beta-Globulins; beta-Thalassemia; Child; Chromosome Deletion; Electrophoresis, Gel, Two-Dimensional; Humans; Malaysia; Mutation; Polymerase Chain Reaction

Topics: Black People; China; Chromosome Deletion; Germany; Globins; Greece; Humans; Italy; Japan; Malaysia; Phenotype; Sicily; Spain; Thalassemia; Turkey; United States