Egyptian Journal of Medical Human Genetics

03/08/2026

🧠 Can CADASIL present with epilepsy?
Although CADASIL is classically associated with stroke, migraine, and cognitive decline, epilepsy can rarely be the presenting feature.

📄 What makes this paper interesting?
🔬 The authors report a 66-year-old woman with focal-onset epilepsy carrying a rare cysteine-sparing NOTCH3 (P572L) mutation.
✅ Seizures as the presenting manifestation
✅ Extensive white matter changes on MRI
✅ Expands the genetic spectrum of CADASIL beyond classic cysteine-altering mutations.

💡 Clinical message
Consider CADASIL in adults with unexplained focal epilepsy and diffuse white matter lesions, even when NOTCH3 variants are cysteine-sparing.
📚 Reference:
Geng Y, et al. Egyptian Journal of Medical Human Genetics. 2026.
https://link.springer.com/article/10.1186/s43042-026-00890-0

29/07/2026

Can combining nutrients be more powerful than taking them individually?
Aging is influenced not only by our genes but also by epigenetic mechanisms that regulate gene expression over time. This review explores how vitamins and plant polyphenols work together to influence DNA methylation, histone modifications, oxidative stress, autophagy, and sirtuin signaling—key pathways involved in healthy aging.
🔗 https://link.springer.com/article/10.1186/s43042-026-00893-x
🔬 Highlights from the review
Rather than evaluating nutrients separately, the review summarizes evidence for several vitamin–polyphenol pairs, including:
🟢 Vitamin C + flavonoids
🟣 Vitamin D + resveratrol
🟠 B-complex vitamins + polyphenolic acids
🟡 Vitamin E + catechins
🟢 Vitamin K2 + polyphenols
These combinations may improve DNA methylation, antioxidant defense, inflammation, autophagy, endothelial function, and cognitive health, although the strength of evidence differs among combinations.
A major strength of this review is that it grades the evidence, clearly distinguishing findings supported by randomized clinical trials from those based mainly on preclinical or observational studies.
💬 Discussion: Should future nutritional recommendations focus on scientifically validated nutrient combinations rather than individual supplements?

Background Aging is a complex biological process influenced by genetic, epigenetic, and environmental factors. Recent advances in nutritional geroscience and epigenomics have revealed that vitamins and plant polyphenols play critical roles in modulating epigenetic mechanisms that regulate aging and....

27/07/2026

Did you know?
Whole-exome sequencing is not only useful for diagnosing monogenic disorders.
It is also a powerful tool for exploring the genetic architecture of complex diseases, especially in populations that remain underrepresented in genomic databases.
In this Algerian Parkinson's disease cohort, researchers identified 73 variants across 22 genes and proposed six candidate genes for future investigation, providing a valuable foundation for Parkinson's disease research in North Africa.
The authors also remind us that variant discovery is only the first step—replication studies, functional validation, and larger cohorts are essential before establishing new gene–disease associations.
📖 Read the full article:
https://link.springer.com/article/10.1186/s43042-026-00895-9

Background Parkinson’s disease (PD), a complex neurodegenerative disorder, is increasingly prevalent, with a strong genetic component. While environmental factors contribute, the exact cause remains elusive. Understanding PD’s genetic basis is vital for advancing research and treatment. This stu...

24/07/2026

Can we stop treating diabetes, obesity, and hypertension as separate diseases?
Patients often present with this triad, yet current therapies typically target each condition individually. In this commentary, the authors introduce the concept of "diabesotension"—the coexistence of diabetes mellitus, obesity, and hypertension—and argue that these conditions share common molecular mechanisms that could be therapeutically targeted.
https://link.springer.com/article/10.1186/s43042-026-00894-w
🔬 What makes this paper interesting?
🧬 By mining NCBI Gene data, the authors identified 443 genes shared among diabetes, obesity, and hypertension.
s43042-026-00894-w.pdf
Among these, AKT1 and NF-κB1 emerged as the only genes involved in all four major pathophysiological hallmarks of diabesotension:
✔️ Insulin resistance
✔️ Chronic inflammation
✔️ Oxidative stress
✔️ Neurohormonal dysregulation
The paper proposes that the PI3K/Akt and NF-κB signaling pathways may represent common therapeutic targets, shifting treatment from managing individual diseases to targeting their shared molecular drivers.
💬 Discussion:
Could future cardiometabolic therapies be designed to target shared molecular pathways, rather than treating diabetes, obesity, and hypertension as separate conditions?

Diabesotension refers to the pathophysiological association between diabetes mellitus, obesity, and hypertension. Despite their frequent coexistence, the underlying molecular mechanisms driving this triad remain poorly understood, and current therapeutic strategies typically address each condition i...

17/07/2026

🧬 Could a simple biochemical test change the diagnostic pathway for children with unexplained neurodegeneration?
X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder, yet its diagnosis is often delayed because of its highly variable clinical presentation. This hospital-based Egyptian study provides a comprehensive clinical, biochemical, and genetic profile of pediatric patients with suspected peroxisomal disorders.
🔗
https://link.springer.com/article/10.1186/s43042-026-00872-2?fbclid=IwVERDUATHapxleHRuA2FlbQIxMABzcnRjBmFwcF9pZAwzNTA2ODU1MzE3MjgAAR6aSt9pe8BdVncEcNLArMsWCiCOa89gOb5U0NdkQH3Q1ZyX6UfyIaBN9SXAig_aem_OTh2EuChT4VsChP431NVbg

Key findings
• 120 high-risk Egyptian children were evaluated. • 6 patients (5%) from 4 unrelated families were diagnosed with X-ALD. • The cerebral phenotype was the most frequent presentation, with white matter demyelination as the predominant MRI finding. • Diagnosis was established using very long-chain fatty acid (VLCFA) analysis followed by ABCD1 gene sequencing. • The study identified three pathogenic ABCD1 variants and one de novo likely pathogenic variant, expanding the molecular spectrum of Egyptian patients.
💬 Discussion:
In children with progressive neurological symptoms and characteristic MRI changes, should VLCFA testing be performed routinely before pursuing broader genomic investigations?

17/07/2026

🧬 Can prenatal genomics redefine the diagnosis of complex fetal anomalies?
When prenatal ultrasound reveals agenesis of the corpus callosum (ACC) together with congenital heart disease, identifying the underlying genetic cause is critical for diagnosis, counseling, and pregnancy management.
A recently published case in the Egyptian Journal of Medical Human Genetics describes a fetus with ACC, Dandy–Walker malformation, complete atrioventricular septal defect, single umbilical artery, and bilateral rocker-bottom feet, in whom whole-exome sequencing identified a novel de novo non-frameshift deletion in SMARCA4, leading to the diagnosis of Coffin–Siris syndrome (CSS4). The study expands the known SMARCA4 variant spectrum and highlights the value of prenatal genomic testing. �
Springer Nature Link
🔗 https://link.springer.com/article/10.1186/s43042-026-00891-z?fbclid=IwVERDUATHagBleHRuA2FlbQIxMABzcnRjBmFwcF9pZAwzNTA2ODU1MzE3MjgAAR6aSt9pe8BdVncEcNLArMsWCiCOa89gOb5U0NdkQH3Q1ZyX6UfyIaBN9SXAig_aem_OTh2EuChT4VsChP431NVbg

Key findings: • Novel de novo in-frame SMARCA4 deletion (c.3439_3450del; p.S1147_F1150del) • Prenatal phenotype included ACC, Dandy–Walker malformation, CAVSD, SUA, and rocker-bottom feet • Conventional karyotype and chromosomal microarray were unrevealing, while whole-exome sequencing established the diagnosis • The report broadens both the genotypic and prenatal phenotypic spectrum of Coffin–Siris syndrome. �
Springer Nature Link
💬 Discussion:
Would you routinely recommend whole-exome sequencing when fetal structural anomalies persist despite normal karyotype and chromosomal microarray?

Background Agenesis of the corpus callosum (ACC) is a birth defect with an incidence of 0.020–0.025% in live births, and is often accompanied by anomalies in the cardiovascular and the musculoskeletal system. ACC is a core phenotype in many syndromes, such as Coffin-Siris syndrome (CSS) whose prom...

14/07/2026

🧬 Rare Cytogenetic Findings in Chronic Myeloid Leukemia (CML)

Hasanova A. et al. | Egyptian Journal of Medical Human Genetics | 2026

This open-access case report describes a patient with CML diagnosed with the Philadelphia chromosome, del(5q), and monosomy 7 simultaneously—an exceptionally rare cytogenetic combination associated with rapid disease progression and resistance to first-line imatinib therapy.

🔬 Key Highlights:
✅ Rare coexistence of three cytogenetic abnormalities at diagnosis.
✅ Primary resistance to imatinib with poor clinical outcome.
✅ Highlights the prognostic value of comprehensive cytogenetic testing.

💡 Clinical Implication: Early identification of additional chromosomal abnormalities may help guide risk stratification and treatment decisions in CML.

📖 Open Access:https://link.springer.com/article/10.1186/s43042-026-00892-y?fbclid=IwVERDUATC3_pleHRuA2FlbQIxMABzcnRjBmFwcF9pZAwzNTA2ODU1MzE3MjgAAR6xyo5De4QJiis5PzgGPGbtWDfSFgt1fV-8fPViDWKOXJahUnDPl8w4xXkM8Q_aem_sNMkaIHI1RvJa21F0LBbPw

12/07/2026

🧬 New Research Published | Egyptian Journal of Medical Human Genetics
Can genetics and geography help explain why some women respond poorly to ovarian stimulation during assisted reproduction?
🔹 Key highlights: • GATA4 rs3203358 was significantly associated with an increased risk of POR. • Age and body weight remained important clinical determinants. • Spatial genetic analyses revealed geographic clustering of POR-associated variants, suggesting that regional genetic diversity may influence ovarian response.
This integrative study demonstrates how combining genetics with computational and spatial approaches can provide new insights into reproductive health and support the future of precision medicine in assisted reproductive technologies.
📖 Read the full article in the Egyptian Journal of Medical Human Genetics.
https://link.springer.com/article/10.1186/s43042-026-00881-1?fbclid=IwY2xjawTAHZFleHRuA2FlbQIxMQBzcnRjBmFwcF9pZAwzNTA2ODU1MzE3MjgAAR7XIvUQv9C9QLt_VMpqKqGIZMEBHLT_s28zCKkABAWL9GXWba6ueVuBQZnxlw_aem_RysRxcHv5U4jZRM5YZoj5w

Background Poor ovarian response (POR) is a major clinical challenge in assisted reproductive technologies (ART), characterized by suboptimal response to ovarian stimulation. While age and environmental factors contribute to POR, genetic determinants, especially within regulatory regions of key repr...

12/07/2026

A newly published case report in the Egyptian Journal of Medical Human Genetics highlights the successful long-term use of growth hormone (GH) therapy in a child with Peters Plus syndrome (PPS) and confirmed growth hormone deficiency, while also documenting rare posterior segment ocular findings.
🔑 Key Highlights
Peters Plus syndrome (PPS) is a rare autosomal recessive disorder caused by pathogenic variants in the B3GLCT gene.
Two years of GH therapy resulted in a marked improvement in growth velocity, demonstrating a favorable efficacy and safety profile.
Long-term follow-up also revealed posterior segment ocular involvement, including bilateral retinal atrophy and retinal detachment, expanding the known clinical spectrum of PPS.
💡 Why This Matters
This case provides valuable evidence that growth hormone therapy may be an effective treatment for children with PPS and confirmed GH deficiency, while emphasizing the importance of comprehensive ophthalmologic surveillance, including evaluation of the posterior segment, in these patients.
Article link:
https://link.springer.com/article/10.1186/s43042-026-00866-0?fbclid=IwY2xjawTAG5hleHRuA2FlbQIxMQBzcnRjBmFwcF9pZAwzNTA2ODU1MzE3MjgAAR5PxafpVOB4w-VU9eBZ_I7OOQ2K1iqsXRHGaW-cXxC4oxhQBc5kQjbRYb4JDQ_aem_voC9Pga47Kd-naWxZrXp3g

Background Peters Plus syndrome (PPS) is an autosomal recessive disorder characterized by a combination of anterior segment abnormalities of the eye, disproportionate short stature, distinctive facial features, and developmental delay caused by a B3GLCT gene mutation. Case presentation A 12-month-ol...

12/07/2026

New Research Published | Egyptian Journal of Medical Human Genetics
Can a single genetic variant increase the risk of familial type 1 diabetes?
A newly published study investigated the PTPN22 C1858T (rs2476601) polymorphism in Moroccan children and adolescents with familial type 1 diabetes.
🔍 Key findings:
The PTPN22 C1858T variant was significantly associated with an increased risk of familial type 1 diabetes.
Both the CT genotype and T allele were more common in affected children than in healthy controls.
Children carrying the TT genotype developed diabetes at ≤5 years of age, suggesting a potential link with earlier disease onset.
This is the first report demonstrating this genetic association in a Moroccan pediatric population.
📌 These findings expand our understanding of the genetic architecture of type 1 diabetes in North African populations and highlight the potential role of PTPN22 in disease susceptibility and early risk assessment. Further large-scale studies are warranted to validate these observations and explore their clinical implications.
Article link:
https://link.springer.com/article/10.1186/s43042-026-00876-y?fbclid=IwY2xjawTAG5hleHRuA2FlbQIxMQBzcnRjBmFwcF9pZAwzNTA2ODU1MzE3MjgAAR5PxafpVOB4w-VU9eBZ_I7OOQ2K1iqsXRHGaW-cXxC4oxhQBc5kQjbRYb4JDQ_aem_voC9Pga47Kd-naWxZrXp3g

Background Type 1 diabetes (T1D) is a lifelong autoimmune condition characterised by the progressive immune-mediated destruction of insulin-secreting β-cells within the pancreatic islets, culminating in absolute insulin deficiency. Genetic susceptibility is a major determinant of disease developmen...