Kadri Karaer

Y chromosome azoospermia factor region microdeletions and recurrent pregnancy loss

OBJECTIVE This study was undertaken to determine the prevalence of Y-chromosome microdeletions in couples with recurrent pregnancy loss (RPL) as compared with fertile couples. STUDY DESIGN Forty-three men from couples with recurrent pregnancy loss, and 43 men from couples with a live birth and no history of miscarriages were recruited from Zekai Tahir Burak Woman Health, Education and Research Hospital. The DNA was tested for the presence of 4 sequence tagged sites (STSs) spanning 4 AZF regions: DYS220 (AZFb), DYS235, DYS236, and DYS237 (AZFd). RESULTS Seven (7) of the 43 men (16%) from couples with recurrent pregnancy loss had microdeletions in 1 or more of the 4 segments studied, whereas none of the fertile men had any microdeletions (P < .05). Their microdeletions were all found specifically at locus DYS 220 (AZFb). CONCLUSION The prevalence of the Y chromosome microdeletion in AZF region was much higher in men from couples with recurrent pregnancy loss than men in fertile couples. This study showed that Y chromosome microdeletion in AZF region may be a possible etiologic factor of recurrent pregnancy loss.

An unexpected finding in a child with neurological problems: mosaic ring chromosome 18

Major neurological disorders may accompany rare chromosomal abnormalities. As an example of this rare condition, we present a case with microcephaly, mental retardation, developmental delay, hyperactivity, stereotypic movements, seizures and dysmorphic facial appearance in whom a mosaic ring chromosome 18 was found [45,XX,-18/46,XX,r(18)/46,XX,dicr(18)]. Although ring chromosome 18 phenotype has been known for a long time, this is the third reported patient with a dicentric ring chromosome 18 mosaicism. The presented case will contribute to the identification of the genotype-phenotype correlation in chromosome 18 anomalies.

Fibrillin-1 gene intron 56 polymorphism in Turkish children with mitral valve prolapse.

OBJECTIVE Mitral valvar prolapse is the most common anomaly of the mitral valve apparatus throughout childhood. Fibrillin is one of the structural components of the elastin-associated microfibrils found in the mitral valve. A case-controlled study has performed to investigate the relationship between fibrillin 1 gene intron 56 polymorphism and risk of mitral valvar prolapse in Turkish children. PATIENTS AND METHODS A total of 77 patients with mitral valvar prolapse diagnosed by clinical evaluation and echocardiography and 89 normal children of same age and sex were studied. The fibrillin-1 gene intron 56 polymorphism was identified by the polymerase chain reaction-based restriction analysis. RESULTS There was a significant difference in the distribution of fibrillin-1 gene intron 56 genotypes (p = 0.0001) and allelic frequency (p = 0.0001) between the cases and the controls. CONCLUSIONS Patients with mitral valvar prolapse have higher frequencies of fibrillin-1 gene intron 56 GC genotypes. Healthy children have higher frequencies of fibrillin-1 gene intron 56 CC genotypes. We speculate that the higher frequency of fibrillin-1 gene intron 56 G-allele increases the risk of mitral valvar prolapse.

Early-Onset Mild Type Leukoencephalopathy Caused by a Homozygous EARS2 Mutation

Childhood leukoencephalopathies are a broad class of diseases, which are extremely rare. The treatment and classification of these disorders are both challenging. Nearly half of children presenting with a leukoencephalopathy remain without a specific diagnosis. Leukoencephalopathy with thalamus and brain stem involvement and high lactate (LTBL) is a newly described childhood leukoencephalopathy caused by mutations in the gene encoding a mitochondrial aminoacyl-tRNA synthetase specific for glutamate, EARS2. Magnetic resonance images show a characteristic leukoencephalopathy with thalamic and brain stem involvement. Here, we report a different clinical course of LTBL supported by typical MRI features in a Turkish patient who presented with a history of failure to walk. The EARS2 gene mutation analysis identified a c.322C>T transition, predicting a p.R108W change. This is the first reported early-onset mild type LTBL caused by a homozygous EARS2 mutation case in the literature.

Novel mutation in SUCLA2 identified on sequencing analysis

Succinate‐CoA ligase, ADP‐forming, beta subunit (SUCLA2)‐related mitochondrial DNA depletion syndrome is caused by mutations affecting the ADP‐using isoform of the beta subunit in succinyl‐CoA synthase, which is involved in the Krebs cycle. The SUCLA2 protein is found mostly in heart, skeletal muscle, and brain tissues. SUCLA2 mutations result in a mitochondrial disorder that manifests as deafness, lesions in the basal ganglia, and encephalomyopathy accompanied by dystonia. Such mutations are generally associated with mildly increased plasma methylmalonic acid, increased plasma lactate, elevated plasma carnitine esters, and the presence of methylmalonic acid in urine. In this case report, we describe a new mutation in a patient with a succinyl‐CoA synthase deficiency caused by an SUCLA2 defect.

A case with de novo inv dup del(8p) associated with dextrocardia and corpus callosum agenesis

Dear Editor, Inverted duplication deletion of 8p [inv dup del(8p)] is a complex chromosome 8 rearrangement with an estimated prevalence of 1/10 000–30 000 in newborns. Floridia et al. proposed the generation of inv dup(8) to be the result of an abnormal pairing of chromosomes 8 at maternal meiosis I followed by an unequal crossover at anaphase I. This causes an asymmetric breakage of the dicentric chromosome that can lead to the formation of an inverted duplicated chromosome and a terminally deleted chromosome. Generally, cases with inv dup del 8p have agenesis of corpus callosum (ACC), hypotonia, mental retardation, dysmorphic features and cardiac findings. We are presenting an inv dup del(8p) case with classical findings. Although, cytogenetic analysis revealed an inverted duplication of 8p, microarray studies confirmed the cytogenetic analysis at a definite breakpoint regions with indicating a deletion at 8p.

Microcephaly and developmental delay caused by short-chain acyl-coa dehydrogenase deficiency

Kılıç M, Şenel S, Karaer K, Ceylaner S. Microcephaly and developmental delay caused by short-chain acyl-CoA dehydrogenase deficiency. Turk J Pediatr 2017; 59: 708-710. We report a four-year-old girl who presented with intrauterine growth retardation, mild dysmorphism, cleft palate, microcephaly, developmental delay, epilepsy and recurrent lower respiratory tract infection and diagnosed short-chain acyl-CoA dehydrogenase deficiency. Metabolic evaluation and molecular analysis confirmed the diagnosis. In spite of many patients already known in literature, this is one of the rarest reports of a Turkish patient. This suggests selective metabolic screening should be done in every patient with unknown etiology of neurological disorder. Furthermore, newborn screening using tandem mass spectrometry may prevent this severe neurological impairment.