High Risk of Gestational Trophoblastic Neoplasia Development in Recurrent Hydatidiform Moles with NLRP7 Pathogenic Variations.

Objective: Pathogenic variations of the NLRP7 and KHDC3L genes are responsible for familial recurrent hydatidiform moles, a rare autosomal recessive phenomenon that can lead to severe comorbidities. Little is known about the diversity of genetic defects or the natural course of disease progression among recurrent hydatidiform mole cases from distinct ethnicities. In this study, we aimed to investigate the mutation profile and pregnancy outcomes in patients with multiple molar pregnancies. Material and Methods: Three unrelated cases with recurrent molar pregnancies are included in this study. None of the patients had a known family history of molar pregnancy. Clinical findings and follow-up results are documented. Sanger sequencing is used to reveal genetic defects in exons and exon-intron boundaries of NLRP7 and KHDC3L genes. Results: NLRP7 pathogenic variants were found in all three cases. In two cases, homozygous, c.2471+1G>A canonical splice cite variant was identified and in one case a homozygous, c.2571dupC (p.Ile858HisfsTer11) frameshift variant was identified. No variant in the KHDC3L gene was found in any case. In all cases, the development of gestational trophoblastic neoplasia complicated the clinical course and the treatment plans. Conclusions: We found that defects of the NLRP7 gene are principally responsible for etiology in our region, and the mutation profile suggests a founder effect in the Turkish population. We suggest early genetic diagnosis and counseling in molar pregnancies and recommend close follow-up in terms of conversion to gestational trophoblastic neoplasia.

Sequencing of the CFTR gene in selected Turkish patients with cystic fibrosis.

AIM: Common mutation detection panels are usually used in clinical practice in most of the centers of our country in order to demonstrate mutations of cystic fibrosis (CF) patients. But heterogenicity of CFTR mutations in Turkey makes identification of CFTR mutations extremely difficult while using common mutation detection panels. METHODS: In this report, we described our experience and findings in offering sequencing of the CFTR gene to 17 patients in which no mutations were identified by common mutation analysis. RESULTS: Overall allele informativity increased from 4/34 (11.76%) to 13/34 (38.2%) after whole exon sequencing of CFTR in our patients. CONCLUSION: Genotype of CF patients could be entirely described in some of our patients by CFTR sequencing but there is still a group of patients, independently from their clinical classification whose mutations can not be determined by CFTR sequencing.

A new case of Martsolf syndrome.

Martsolf syndrome is an autosomal recessive syndrome characterized by microcephaly, mental retardation, cataract, hypogonadism and short stature. A seven-year-old boy was admitted to the hospital with growth retardation and difficulties in walking. His parents were first cousins. Bilateral lens extraction was performed during infancy because of congenital cataract. On physical examination he had short stature, microcephaly, micropthalmia, hypogonadism, mental retardation. Brain magnetic resonance imaging revealed alterations in the white matter. Up to date very few cases with this syndrome have been reported. This is the first case described in the Turkish population and may add valuable information to the literature.

Trends in cytogenetic prenatal diagnosis in a reference hospital in Izmir/Turkey: a comparative study for four years.

The aim of the study was to investigate the major changes in the indications, culture success and abnormality rate for conventional cytogenetic prenatal diagnosis on amniotic fluid samples between the period of January 1998 and December 2001 in Izmir. The cytogenetic laboratory provides a prenatal service to obstetrics-gynecology departments of different hospitals in Izmir. A limited number of patients (6-8 per week) is randomly accepted for prenatal cytogenetic study. Over the 4 years period 1190 prenatal cytogenetic tests were performed in our center. The most common indication was advanced maternal age for each year. However its rate has increased significantly within the years (35.68% in 1998, 61.38% in 2001), while the rate of both triple test and ultrasound scanning indications decreased. Culture success rates have improved (97.97% in 1998, 99.74% in 2001). Comparing the first two years to the last two years the rate of abnormal cytogenetic results decreased significantly (3.83% in 1998-99, 2.48% in 2000-01). The major reason for this decrease is probably related to the changes in indications throughout the years.

Paracentric inversion in the short arm of chromosome 1. Report of a family and review of the literature.

In general, carriers of paracentric inversions are phenotypically normal, although individual reports describe like occurrence of infertility, miscarriages and mental retardation in inversion carriers. We present a family with paracentric inversion of 1p [karyotype: 46,XY/XY, inv(1)(p13.2p36.2)] in 7 of the 12 investigated family members. The index patient, a four year-old boy was referred for motor and mental retardation. The possible relationship between the paracentric inversion and the MR/MCA syndrome in the index patient of this family is briefly discussed.