The Frequency and Spectrum of Chromosomal Translocations in a Cohort of Sri Lankans

Abstract

Translocations are the most common type of structural chromosomal abnormalities. Unbalanced translocations are usually found in children who present with congenital abnormalities, developmental delay, or intellectual disability. Balanced translocations are usually found in adults who frequently present with reproductive failure; either subfertility, or recurrent pregnancy loss. Herein, we report the spectrum and frequency of translocations in a Sri Lankan cohort. A database of patients undergoing cytogenetic testing was maintained prospectively from January 2007 to December 2016 and analyzed, retrospectively. A total of 15,864 individuals were tested. Among them, 277 (1.7%) had translocations. There were 142 (51.3%) unbalanced translocations and 135 (48.7%) balanced translocations. Majority (160; 57.8%) were Robertsonian translocations. There were 145 (52.3%) children and adolescents aged less than 18 years with translocations, and 142 (97.9%) were unbalanced translocations. Majority [138 (95.2%)] were referred due to congenital abnormalities, developmental delay, or intellectual disability, and 91 were children with translocation Down syndrome. All adults aged 18 years or above (132) had balanced translocations. Subfertility and recurrent pregnancy loss [84 (63.6%)] and offspring(s) with congenital abnormalities [48 (36.4%)] were the most common indications in this group. Majority (68.2%) in this group were females with reciprocal translocations (55.3%). Chromosomes 21, 14, and 13 were the most commonly involved with rob(14q21q) [72 (26%)], rob(21q21q) [30 (13.7%)], and rob(13q14q) [34 (12.3%)] accounting for 52% of the translocations. Chromosomes 1, 8, 11, and 18 were most commonly involved in reciprocal translocations. The observed high frequency of chromosomal translocations in our cohort highlights the importance of undertaking cytogenetic evaluation and providing appropriate genetic counseling for individuals with the phenotypes associated with these translocations.

Relato de uma menina com cromossomo derivativo 4 resultante de translocação herdada paterna t(4:18)

“…Geralmente, um dos (ou ambos) progenitores não apresentam manifestações fenotípicas mas levam a produzir tanto gametas normais quanto gametas anormais, devido aos diferentes gametas produzidos durante a gametogênese 9,14 . Esses progenitores tem um risco exacerbado de anormalidades reprodutivas incluindo infertilidade, abortamentos de repetição e descendentes com cariótipo desbalanceado com efeito fenotípico 3,14 .…”

“…Comumente, a translocação pode estar relacionada com o surgimento de cromossomo derivativo 3 . O cromossomo derivativo (der) é representado por um cromossomo rearranjado estruturalmente, abrangendo um ou mais cromossomos ou de mais de um rearranjo no mesmo cromossomo 4 .…”

Implicaciones causadas por la presencia y segregación de translocaciones robertsonianas. Su diagnóstico y efectos en la población

“…Todos los individuos mayores de 18 años (132) tenían translocaciones balanceadas (90 mujeres, lo que las hizo mayoria con 68.2 %), 84 de ellos han tenido problemas de fertilidad y 48 han tenido descendencia con anormalidades congénitas. Los cromosomas 21, 14 y 13 fueron los más involucrados en las translocaciones robertsonianas; 72 individuos (45%) portaban der (14q;21q), 30 (18.7 %) portaban der(21q;21q) y 34 (21.25%) portaban der(13q;14q) (43).…”

Analysis of the embryos genetic characteristics and methodologies of human translocations research

“…Представленные C. S. Paththinige et.al. (2019) результаты анализа выборки пациентов (n=15864) показали сходную частоту транслокаций -1,7 %, соотношение роберстсоновские/реципрокные -57,8/42,2 % [15]. В США частота сбалансированных транслокаций среди населения в настоящее время оценивается как 1:500 [16], или 0,2 %.…”