Browsing by Author "Temel, Sehime G."

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A Novel TBX19 Gene Mutation in a Case of Congenital Isolated Adrenocorticotropic Hormone Deficiency Presenting with Recurrent Respiratory Tract Infections
(FRONTIERS MEDIA SA, 2017-01-01) Akcan, Nese; Serakinci, Nedime; Turkgenc, Burcu; Bundak, Ruveyde; Bahceciler, Nerin; Temel, Sehime G.
Introduction: Congenital isolated adrenocorticotropic hormone deficiency (CIAD) is a rare disease characterized by low adrenocorticotropic hormone (ACTH) and cortisol levels. To date, recurrent pulmonary infections in infancy have not been reported as an accompanying symptom of CIAD. Case presentation: A 7-year-old boy was hospitalized nine times for recurrent lower respiratory tract infections. The results of all tests for the possible causes of wheezing were within the normal limits. His ACTH and cortisol levels were persistently low. All other pituitary hormone levels, and adrenal ultrasound and pituitary magnetic resonance imaging results, were normal. Molecular analyses confirmed the diagnosis of CIAD by identifying compound heterozygosity for two mutations in the TBX19 gene. The first was a novel frameshift c. 665delG variant in exon 4 of the TBX19 gene, leading to premature termination that was predicted to result in a non-functional truncated protein. The second was a nonsense C-to-T transition in exon 6 of the TBX19 gene, resulting in an arg286-to-ter mutation (dbSNP: rs74315376). Both parents were heterozygous for one of the mutations. Conclusion: Here, we presented a new mutation in the TBX19 gene in a patient with CIAD who presented with recurrent respiratory tract infections. This expands the mutation spectrum in this disorder. To conclude, adrenal insufficiency should be considered in patients with unexplained recurrent infections to prevent a delay in diagnosis.
Bi-allelic Mutations in M1AP Are a Frequent Cause of Meiotic Arrest and Severely Impaired Spermatogenesis Leading to Male Infertility
(CELL PRESS, 2020-01-01) Wyrwoll, Margot J.; Temel, Sehime G.; Nagirnaja, Liina; Oud, Manon S.; Lopes, Alexandra M.; van der Heijden, Godfried W.; Heald, James S.; Rotte, Nadja; Wistuba, Joachim; Woeste, Marius; Ledig, Susanne; Krenz, Henrike; Smits, Roos M.; Carvalho, Filipa; Goncalves, Joao; Fietz, Daniela; Turkgenc, Burcu; Ergoren, Mahmut C.; Cetinkaya, Murat; Basar, Murad; Kahraman, Semra; McEleny, Kevin; Xavier, Miguel J.; Turner, Helen; Pilatz, Adrian; Roepke, Albrecht; Dugas, Martin; Kliesch, Sabine; Neuhaus, Nina; Aston I, Kenneth; Conrad, Donald F.; Veltman, Joris A.; Friedrich, Corinna; Tuettelmann, Frank; Consortium, G. E. M. I. N. I.
Male infertility affects similar to 7\% of men, but its causes remain poorly understood. The most severe form is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis. So far, only a few validated disease-associated genes have been reported. To address this gap, we performed whole-exome sequencing in 58 men with unexplained meiotic arrest and identified the same homozygous frameshift variant c.676dup (p.Trp226LeufsTer4) in M1AP, encoding meiosis 1 associated protein, in three unrelated men. This variant most likely results in a truncated protein as shown in vitro by heterologous expression of mutant M1AP. Next, we screened four large cohorts of infertile men and identified three additional individuals carrying homozygous c.676dup and three carrying combinations of this and other likely causal variants in M1AP. Moreover, a homozygous missense variant, c.1166C>T (p.Pro389Leu), segregated with infertility in five men from a consanguineous Turkish family. The common phenotype between all affected men was NOA, but occasionally spermatids and rarely a few spermatozoa in the semen were observed. A similar phenotype has been described for mice with disruption of M1ap. Collectively, these findings demonstrate that mutations in M1AP are a relatively frequent cause of autosomal recessive severe spermatogenic failure and male infertility with strong clinical validity.
Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell and Lange-Nielsen syndrome: case reports
(BIOMED CENTRAL LTD, 2017-01-01) Uysal, Fahrettin; Turkgenc, Burcu; Toksoy, Guven; Bostan, Ozlem M.; Evke, Elif; Uyguner, Oya; Yakicier, Cengiz; Kayserili, Hulya; Cil, Ergun; Temel, Sehime G.
Background: Jervell and Lange-Nielsen syndrome (JLNS) isa recessive model of long QT syndrome which might also be related to possible hearing loss. Although the syndrome has been demonstrated to be originated from homozygous or compound heterozygous mutations in either the KCNQ1 or KCNE1 genes, additional mutations in other genetic loci should be considered, particularly in malignant course patients. Case presentations: Three patients were admitted into hospital due to recurrent seizures/syncope, intrauterine and postnatal bradycardia respectively
STUB1 polyadenylation signal variant AACAAA does not affect polyadenylation but decreases STUB1 translation causing SCAR16
(WILEY, 2018-01-01) Turkgenc, Burcu; Sanlidag, Burcin; Eker, Amber; Giray, Asli; Kutuk, Ozgur; Yakicier, Cengiz; Tolun, Aslihan; Temel, Sehime G.
We present three siblings afflicted with a disease characterized by cerebellar ataxia, cerebellar atrophy, pyramidal tract damage with increased lower limb tendon reflexes, and onset of 31 to 57 years, which is not typical for a known disease. In a region of shared homozygosity in patients, exome sequencing revealed novel homozygous c.{*}240T>C variant in the 3'UTR of STUB1, the gene responsible for autosomal recessive spinocerebellar ataxia 16 (SCAR16). In other genes, such an alteration of the evolutionarily highly conserved polyadenylation signal from AATAAA to AACAAA is known to highly impair polyadenylation. In contrast, RNA sequencing and quantification revealed that neither polyadenylation nor stability of STUB1 mRNA is affected. In silico analysis predicted that the secondary structure of the mRNA is altered. We propose that this change underlies the extremely low amounts of the encoded protein in patient leukocytes.