Cases of hypogonadotropic hypogonadism: A single-center experience.

Background: Delayed puberty (DP) affects approximately 2% of adolescents. In most patients of both genders, delayed puberty is due to constitutional delay in growth and puberty (CDGP); it is a self-limiting condition starting later than usual during puberty but progressing normally. Other causes of DP include permanent hypogonadotropic hypogonadism, functional hypogonadotropic hypogonadism, and gonadal insufficiency. Methods: Nine patients admitted to the Ankara Atatürk Sanatoryum Training and Research Hospital Pediatric Endocrinology Department with hypogonadotropic hypogonadism between January 2012 and December 2022 were analyzed. Results: Nine patients who applied to our pediatric endocrinology clinic with delayed puberty were analyzed. These nine patients were diagnosed and reported as hypogonadotropic hypogonadism with molecular methods. We aimed to determine the status of these cases from a molecular point of view, to emphasize the importance of hypogonadotropic hypogonadism in patients with delayed puberty, and to reveal the rarely encountered delayed puberty together with the clinical and laboratory data set of the patients. Conclusions: To emphasize the importance of hypogonadotropic hypogonadism, which is a rare cause of delayed puberty, the molecular predispositions of our patients followed in our clinic are reviewed, and the data we have provided will contribute to the accumulation of data in this area.

A New Splice-site Mutation of SPINK5 Gene in the Netherton Syndrome with Different Clinical Features: A Case Report.

Netherton syndrome (NS) is a rare genodermatosis characterized by the triad of ichthyosiform erythroderma, hair shaft abnormality and an atopic diathesis. We report a case of a 20-year-old male patient presented with pruritus, decreased sweat secretion and generalized erythema on his body. Netherton syndrome is caused by mutations in the SPINK5 gene that is a crucial role for epidermal barrier function in the skin. Different clinical and phenotypical features can occur based on various LEKTI-domains mutations. Diagnosis is made by the atopic story, hair shaft abnormality, cutaneous lesions and identification of the SPINK5 gene mutation. In our patient, we detected a new splice site mutation in the SPINK5 gene and pili annulati as hair abnormality. Affected patients are usually misdiagnosed because of cutaneous lesions such as atopic dermatitis. Therefore, each clinical finding should be evaluated together. We aimed to present a case with a new SPINK5 gene mutation and different clinical features in NS.

An eight-case 1q21 region series: novel aberrations and clinical variability with new features.

BACKGROUND: Rearrangement of the 1q21 region of chromosome 1 manifests as multiple phenotypes, including microcephaly, intellectual disability, dysmorphic facial features, eye abnormalities, cardiac defects, genitourinary anomalies, autism spectrum disorder, psychiatric conditions and seizures. Herein, we describe eight patients with 1q21 deletion and duplication syndromes, and novel deletions and findings. METHODS: Chromosomal microarray analysis was performed to identify the existence of copy number variation. Quantitative polymerase chain reaction was applied using specific primers for the control and 1q21 region of chromosome 1. Mutational analysis was performed in case 5 using direct genomic sequencing for exons 1-6 in RBM8A. RESULTS: Copy number variation analysis identified seven deletions and one duplication of the 1q21 region in the eight patients. In addition, four variations were de novo, and two deletions are reported here for the first time. One of the cases (case 7) presents moderate intellectual disability and dysmorphic facial findings, whereas chromosomal microarray analysis showed that case 7 had an 889-kb deletion in the 1q21 proximal region (GPR89A, PDZK1, CD160, POLR3C and NBPF12). CONCLUSION: Although the deletion in case 5 did not include the thrombocytopenia-absent radius syndrome critical region or the RBM8A gene, he had pectoral muscle hypoplasia, radius and humerus hypoplasia and short curved ribs, which are indicative of a potential thrombocytopenia-absent radius region modifier. The findings in case 7 suggest that the proximal part of the 1q21 microdeletion syndrome region might be very important for the onset of clinical manifestations. Some novel findings were observed in the presented cases, such as radius and humerus hypoplasia and brain stem hypoplasia. The presented findings expand the spectrum of 1q21 aberrations and provide evidence of genotype-phenotype correlations for this region.

Mitochondrial DNA copy number alterations in familial mediterranean fever patients.

OBJECTIVES AND BACKGROUND: Familial Mediterranean Fever (FMF) is characterized by recurrent fever episodes as a result of inflammation of serous membranes. Changes in the number of different mtDNA copy number variations, detected in FMF patients, who developed amyloidosis, might be an important parameter in the understanding of the pathophysiology of the disease. METHODS: Changes in the mtDNA copy number between 50 patients with FMF, who had M694V homozygote mutation and amyloidosis, and 50 healthy controls, who had not any MEFV mutation or FMF clinical finding, were examined. The 22 MEFV mutations were analyzed by Pyromark Q24 system. Quantitative analysis was performed on RT-PCR. The level of mtDNA was calculated using the delta Ct (ΔCt) of average Ct of mtDNA and nDNA (ΔCt = Ct mtDNA-Ct nDNA) in the same well as an exponent of 2 (2ΔCt). RESULTS: A significant decrease in the amount of mtDNA was detected in FMF patients with M694V homozygous mutation carriers, who developed amyloidosis compared to the control group (p < 0.001). CONCLUSION: In this study, mitochondrial dysfunction, which has been identified through changes in the mitochondrial genome in many diseases, was identified by showing that the copy number variations of mtDNA in leukocytes also decreased for FMF disease (Tab. 3, Fig. 1, Ref. 21).