Nazli Busra Acikgoz

Purpose: This study investigated the effects of ketogenic diet (KD) intervention on the cortical proteome in genetic absence epilepsy rats from Strasbourg (GAERS), a well‐established model of absence epilepsy. The ketogenic diet is a therapeutic intervention for epilepsy, yet its mechanisms remain incompletely understood. Method: Thirty‐day‐old male GAERS rats were fed a KD (88.8% fat, 10.2% protein, 1% carbohydrate; n = 4) or a normal diet (ND; n = 3), with Wistar rats ( n = 3) as healthy controls. A shotgun proteomics approach with data‐dependent acquisition (DDA) was used to analyze the somatosensory cortex (SCx), a key cortical driver of absence seizures. Data were processed with MaxQuant and Perseus. Findings: Compared to Wistars, GAERS‐ND rats showed significant alterations in 526 proteins in SCx and KD treatment significantly altered 121 proteins in SCx of GAERS. Notably, KD was associated with partial shifts in the expression patterns of 22 proteins toward those observed in Wistar controls. Most KD‐affected proteins were synaptic (72% SCx) and mitochondrial. Pathway analysis indicated that ketogenic diet–associated protein changes were enriched in axon guidance, neurodevelopment, and metabolic pathways in the somatosensory cortex. Conclusion: Together, these results suggest that synaptic and mitochondrial protein alterations in this region are associated with cortical molecular adaptations observed under ketogenic diet administration in absence epilepsy.

Background. Stuve–Wiedemann syndrome is a rare autosomal recessive bent-bone dysplasia characterized by dysautonomia and distinctive skeletal abnormalities, most commonly caused by biallelic LIFR variants. Methods. Eleven patients from ten unrelated families with molecularly confirmed Stuve–Wiedemann syndrome were evaluated. Detailed demographic, perinatal, clinical, radiographic, and molecular data were collected. All patients underwent Sanger sequencing of LIFR. Results. Respiratory problems and episodic hyperthermia were present in all patients, while feeding difficulties, hypotonia, growth failure, developmental delay, craniofacial dysmorphism, oral abnormalities, and ocular involvement were also common. All patients demonstrated long-bone bowing, cortical thickening, and flared metaphyses. A biallelic LIFR variant was identified in all patients, occurring in the homozygous state in nine patients and in the compound heterozygous state in two patients. The recurrent c.2074C>T; p.(Arg692Ter) variant was homozygous in seven patients and compound heterozygous in one patient. Three novel LIFR variants were also identified. Conclusion. Stuve–Wiedemann syndrome is characterized by a high mortality rate during the first two years of life due to severe dysautonomia, and orthopedic complications worsen progressively with age; therefore, early diagnosis and lifelong multidisciplinary follow-up are essential. Furthermore, the high rate of consanguinity in Türkiye, together with the recurrent p.(Arg692Ter) variant in LIFR identified in multiple unrelated families, supports the possibility of a founder effect and suggests that the frequency of Stuve–Wiedemann syndrome in our population may be higher than expected. Our findings further characterize the previously reported clinical manifestations of Stuve–Wiedemann syndrome while expanding the molecular spectrum through the identification of three novel LIFR variants.

Fibrodysplasia ossificans progressiva (FOP) is a rare multisystem disorder with the triad of congenital hallux valgus, flare-ups and progressive heterotopic ossification. The flare-ups (episodes of painful soft-tissue swelling) start in early childhood, and progress to ossification with cumulative functional disability. We describe the cohort of FOP from a single tertiary center in Türkiye and highlight the phenotypic variabilities and diagnostic pitfalls. The subjects included 10 affected individuals (7 females and 3 males, aged 10 days to 20 years), whose diagnosis was confirmed with molecular tests, including full ACVR1 sequencing, targeted hotspot analysis, a gene panel for skeletal disorders, and whole-exome sequencing. Clinical and imaging data were retrospectively reviewed. The common pathogenic variant of FOP, c.617G > A, p.(Arg206His) of ACVR1 , was found in 9 patients, while a rare variant, c.983G > A, p.(Gly328Glu) in one. All patients with the common variant exhibited the classical triad of FOP. Other morbidities included limited cervical mobility in 8, temporomandibular joint involvement in 4, scoliosis in 6, scalp nodules in 6, and brain anomalies in 2. Scalp nodules could be a transient finding with spontaneous regression and were an early manifestation in 2. One patient showed a distinctive brain malformation of FOP (pontine dysmorphism with fusion of the facial colliculi and dorsal bulging into the fourth ventricle). Four patients underwent biopsy prior to referral to our institution. One was coincidentally associated with Ewing sarcoma. The infant with the rare variant presented with limb reduction defects and brain malformation and had not yet developed flare-ups or heterotopic ossification. Conclusion : This single-center cohort from Türkiye confirms the key clinical features of FOP associated with both common and rare ACVR1 variants and expands the radiological findings with notable features such as pontine malformation. It also highlights scalp nodules as a potential early diagnostic clue, emphasizing the importance of early clinical recognition and timely molecular confirmation, while providing insights that may inform future therapeutic approaches. What Is Known: • Fibrodysplasia ossificans progressiva (FOP) is caused by activating variants in ACVR1, most commonly c.617GA, p.(Arg206His), and is characterized by congenital hallux valgus, flare-ups, and progressive heterotopic ossification • Early diagnosis is challenging, and misdiagnosis may lead to harmful invasive procedures such as biopsies. What Is New: • This single-center cohort confirms the key features of FOP, expands the radiological spectrum (including pontine malformation), and identifies scalp nodules as an early diagnostic clue.

Background: Triple X syndrome is the most common sex chromosome aneuploidy in females; however, due to the subtlety of clinical findings, only a small proportion of affected individuals are diagnosed. This study presents the demographic, clinical, and cytogenetic characteristics of patients with Triple X syndrome followed at a single center. Methods: We retrospectively reviewed the medical records of patients diagnosed with Triple X syndrome at our department between 2008 and 2025. Demographic characteristics, clinical findings including anthropometric measurements, dysmorphic features, associated anomalies, endocrine and neurodevelopmental findings, and cytogenetic results were analyzed. Results: The study included a total of 20 patients diagnosed with Triple X syndrome, 13 of whom (65%) had a non-mosaic 47,XXX karyotype and 7 (35%) had mosaic chromosomal abnormalities. Four patients received a prenatal diagnosis, four were diagnosed in adulthood, and the remaining patients were diagnosed during childhood. Dysmorphic features; neurodevelopmental problems such as developmental delay, intellectual disability, and attention-deficit/ hyperactivity disorder; as well as cardiac defects and endocrine disorders were the main characteristics observed in the patients. Conclusion: Triple X syndrome is a relatively common chromosomal disorder, which should be considered in patients who experience congenital anomalies, neurodevelopmental abnormalities, and reproductive problems. Variable and subtle findings should be carefully considered, bearing in mind that mosaic cases may present with diverse and overlapping phenotypes.

We report two siblings harboring a homozygous MGME1 variant, NM_052865.4:c.818 T>A; p.(Val273Glu), both presenting with ptosis, myopathy, scoliosis, and gastrointestinal symptoms. The index patient developed progressive, medically refractory dilated cardiomyopathy and underwent successful orthotopic heart transplantation (OHT). Reanalysis of previously negative WES identified the variant in the index case, and segregation by Sanger sequencing confirmed homozygosity in both siblings. Although several clinical findings overlap with previously described MGME1 ‐related disease, the detected variant remains classified as a variant of uncertain significance (VUS); thus, functional evidence is needed to better understand its potential causal relevance. Additionally, this report underscores the importance of periodic genomic data reanalysis and highlights the variable expressivity that may occur even within the same family.

This study investigates the effects of a ketogenic diet (KD) on the brain proteome in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a model of genetic absence epilepsy. The ketogenic diet is a therapeutic intervention for epilepsy, yet its mechanisms remain incompletely understood. Thirty-day-old male GAERS rats were fed a KD (88.8% fat, 10.2% protein, 1% carbohydrate; n = 4) or a normal diet (ND; n = 3), with Wistar rats (n = 3) as healthy controls. A shotgun proteomics approach with data-dependent acquisition was used to analyze the somatosensory cortex (SCx) and hippocampus (Hipp). Data were processed with MaxQuant and Perseus. Compared to Wistars, GAERS-ND rats showed significant alterations in 526 proteins in SCx and 612 in Hipp. KD treatment significantly altered 122 proteins in SCx and 124 in Hipp of GAERS. Notably, KD reversed the expression of 22 proteins in SCx and 32 in Hipp to levels observed in controls. Most KD-affected proteins were synaptic (72% SCx, 76.6% Hipp) and mitochondrial. Pathway analysis indicated KD regulates axon guidance, neurodevelopment, and metabolism in SCx, and autophagy, mitophagy, and Rho GTPase signaling in Hipp. The workflow of the experimental design is provided in Fig. 1.