Cytogenetic Profiles of Clinically Diagnosed Down Syndrome (DS) Cohort Reported at a Single Centered Accredited Laboratory in Sri Lanka
Laboratory Genetics and Genomics
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Primary Categories:
- Laboratory Genetics
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Secondary Categories:
- Laboratory Genetics
Introduction:
Down Syndrome (DS) is a congenital disorder characterized by distinctive phenotypic features due to the presence of an extra copy of chromosome 21. It is one of the most common surviving aneuploidies reported, accounting for approximately 1 in 700 newborns. This disorder results from three types of chromosomal anomalies: trisomy 21 due to non-disjunction, translocation, and mosaicism.
DS represents a spectrum of phenotypical presentations directly associated with chromosomal anomalies. Three complete copies of chromosome 21 (trisomy 21), which represent 95% of reported DS cases, occur due to non-disjunction meiosis during gamete formation.
Translocation DS occurs due to the presence of an extra chromosome 21 rearranged with either chromosome 13, 14, 15, 21, or 22. Translocation DS represents approximately 4% of reported DS cases with the highest prevalence with chromosomes 14 and 21. Mosaicism in DS is characterized by the presence of trisomy 21 in a subset of cells, while the remaining cells have a normal chromosome complement and occur in approximately 1% of cases.
Peripheral blood karyotype is considered the gold standard in the diagnosis of DS patients and the test outcome is extremely useful in effective patient management. A single-centered cytogenetic laboratory accredited by the College of American Pathologists conducted the present study with a scope of understanding the cytogenetic diversity of the clinically diagnosed DS cohort in Sri Lanka reported for six years commencing from 2018.
Methods:
Peripheral blood karyotype was carried out by harvesting cultured lymphocytes in vitro according to the protocol originally described by Moorhead et al., 1960. A total of 20 metaphases with GTG banded chromosomes per sample were analyzed and karyotype was reported in accordance with the International System for Cytogenetic Nomenclature (ISCN).
Results:
The clinically diagnosed DS cohort in the present study consists of 383 participants with a male prominence (52.74%). Among the diagnosed DS cohort, 92.17% of participants reported the existence of an additional free complete chromosome 21 (trisomy 21), while 5.2% of participants reported translocation DS with predominant involvement with chromosomes 14 and 21. Furthermore, 2.61% of participants exhibited mosaicism for trisomy 21.
Conclusion:
The outcome of the present study confirms the existence of free additional complete chromosome 21 as the predominant chromosomal anomaly among the reported DS cohort in Sri Lanka. Other chromosomal anomalies, such as translocations and mosaicism have a lesser impact on the reported cohort, thus well supported by the previously reported prevalence data among different patient cohorts. Further, the findings of the present study underscore the necessity for karyotyping for all individuals clinically diagnosed with Down syndrome to provide appropriate patient management and genetic counseling.
Down Syndrome (DS) is a congenital disorder characterized by distinctive phenotypic features due to the presence of an extra copy of chromosome 21. It is one of the most common surviving aneuploidies reported, accounting for approximately 1 in 700 newborns. This disorder results from three types of chromosomal anomalies: trisomy 21 due to non-disjunction, translocation, and mosaicism.
DS represents a spectrum of phenotypical presentations directly associated with chromosomal anomalies. Three complete copies of chromosome 21 (trisomy 21), which represent 95% of reported DS cases, occur due to non-disjunction meiosis during gamete formation.
Translocation DS occurs due to the presence of an extra chromosome 21 rearranged with either chromosome 13, 14, 15, 21, or 22. Translocation DS represents approximately 4% of reported DS cases with the highest prevalence with chromosomes 14 and 21. Mosaicism in DS is characterized by the presence of trisomy 21 in a subset of cells, while the remaining cells have a normal chromosome complement and occur in approximately 1% of cases.
Peripheral blood karyotype is considered the gold standard in the diagnosis of DS patients and the test outcome is extremely useful in effective patient management. A single-centered cytogenetic laboratory accredited by the College of American Pathologists conducted the present study with a scope of understanding the cytogenetic diversity of the clinically diagnosed DS cohort in Sri Lanka reported for six years commencing from 2018.
Methods:
Peripheral blood karyotype was carried out by harvesting cultured lymphocytes in vitro according to the protocol originally described by Moorhead et al., 1960. A total of 20 metaphases with GTG banded chromosomes per sample were analyzed and karyotype was reported in accordance with the International System for Cytogenetic Nomenclature (ISCN).
Results:
The clinically diagnosed DS cohort in the present study consists of 383 participants with a male prominence (52.74%). Among the diagnosed DS cohort, 92.17% of participants reported the existence of an additional free complete chromosome 21 (trisomy 21), while 5.2% of participants reported translocation DS with predominant involvement with chromosomes 14 and 21. Furthermore, 2.61% of participants exhibited mosaicism for trisomy 21.
Conclusion:
The outcome of the present study confirms the existence of free additional complete chromosome 21 as the predominant chromosomal anomaly among the reported DS cohort in Sri Lanka. Other chromosomal anomalies, such as translocations and mosaicism have a lesser impact on the reported cohort, thus well supported by the previously reported prevalence data among different patient cohorts. Further, the findings of the present study underscore the necessity for karyotyping for all individuals clinically diagnosed with Down syndrome to provide appropriate patient management and genetic counseling.