The Complex Genetic Landscape of Hereditary Ataxias in Turkey and Implications in Clinical Practice.

BACKGROUND: The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations. OBJECTIVE: To identify the prevalence and genetic structure of hereditary ataxias in the Turkish population. METHODS: Our cohort consisted of 1296 index cases and 324 affected family members. Polymerase chain reaction followed by Sanger sequencing or fragment analysis were performed to screen for the trinucleotide repeat expansions in families with a dominant inheritance pattern, as well as in sporadic cases. The expansion in the frataxin (FXN) gene was tested in all autosomal recessive cases and in sporadic cases with a compatible phenotype. Whole-exome sequencing was applied to 251 probands, selected based on the family history, age of onset, and phenotype. RESULTS: Mutations in known ataxia genes were identified in 30% of 1296 probands. Friedreich's ataxia was found to be the most common recessive ataxia in Turkey, followed by autosomal recessive spastic ataxia of Charlevoix-Saguenay. Spinocerebellar ataxia types 2 and 1 were the most common dominant ataxias. Whole-exome sequencing was performed in 251 probands with an approximate diagnostic yield of 50%. Forty-eight novel variants were found in a plethora of genes, suggesting a high heterogeneity. Variants of unknown significance were discussed in light of clinical data. CONCLUSION: With the large sample size recruited across the country, we consider that our results provide an accurate picture of the frequency of hereditary ataxias in Turkey. © 2021 International Parkinson and Movement Disorder Society.

The birth of a baby with mosaicism resulting from a known mosaic embryo transfer: a case report.

Mosaic embryos have the potential to implant and develop into healthy babies. The transfer of mosaic embryos is now considered to be a possible option for women undergoing ART with preimplantation genetic testing for aneuploidies and in the absence of euploid embryos, particularly those with diminished ovarian reserve and/or advanced maternal age. It can aid in avoiding the discard of potentially viable embryos, which might otherwise result in healthy babies. In over 500 studies on mosaicism, there have been no reports of mosaicism in babies born following the transfer of mosaic embryos. Here, we present a case report of a 39-year-old woman with diminished ovarian reserve with only one blastocyst available for trophectoderm biopsy. The transfer of the embryo, which showed 35% mosaicism of monosomy 2, resulted in pregnancy. Amniocentesis revealed a mosaic trisomic mos46,XX(98)/47,XX,+2(2) karyotype. There were no pathological findings in detailed ultrasonography, and the fetus showed a normal fetal growth with no evidence of intrauterine growth retardation. A healthy female baby was born at Week 37. The peripheral blood chromosome analysis validated with fluorescence in situ hybridization showed 2% mosaic monosomy 2 [mos45,XX,-2(2)/46,XX(98)]. This is the first reported case of true fetal mosaicism resulting in a live birth following the transfer of a known mosaic embryo. Worldwide, prenatal diagnosis has shown the depletion of mosaicism in embryos transferred after they have been reported as mosaics. Our case demonstrates the need for close prenatal monitoring and diagnosis by early amniocentesis, preferably at >14 weeks gestation.

Conforming with current regulation in Turkey regarding the freezing of oocytes: A case report of the first pregnancy in Turkey achieved through oocyte vitrification.

OBJECTIVES: To present the first pregnancy achieved in Turkey with frozen-warmed oocytes in a case with previous nine unsuccessful assisted reproductive technology (ART) attempts. METHODS: The clinical follow-up of a 33-year-old female applying to our ART centre after a long and complicated history of infertility is described. RESULTS: In April 2013, the woman attempted our centre for her 10th ART trial. She informed us on oocyte pick-up (OPU) day that her husband had been hospitalized following a car crush in Albania and was unable to travel to our clinic to give a sperm sample. We were therefore placed in the position of having to make an emergency decision. OPU was done and seven oocytes were retrieved. Six metaphase II (MII) oocytes out of seven Cumulus Oocyte Complexes (COCs) were vitrified using the Kitazato Vitrification Cryotop Kit. Six months later, in November 2013, the patient applied for transfer. Two blastocysts were transferred and the ART trial resulted with a singleton pregnancy and the birth of a healthy new-born at term via cesarean section. CONCLUSION: Regulation Codes on Assisted Reproductive Procedures and Assisted Reproductive Technology Centres, published in the Official Gazette of the Republic of Turkey, on 6 March 2010 forbade the freezing of gonad cells and tissues except when essential for medical reasons and stated that this would be specified later. However, the Regulation Codes published in the Official Gazette of the Republic of Turkey, on 30 September 2014 provided no further clarification. Unfortunately, the wording of the regulations did not specifically address this unexpected emergency situation. However, we saw our decision to cryopreserve the oocytes as a valid interpretation of the regulations, bearing in mind also the requirement that sperm and oocyte in the IVF process must be those of a married couple. Turkish medicolegal regulations should be revised to increase the chances of more women taking advantage of the procedure to preserve their reproductive autonomy and to give guidance on what action may be taken in emergency situations.