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Autism genetics.

Autism spectrum disorder (ASD) is a severe neuropsychiatric disease with strong genetic underpinnings. However, genetic contributions to aut … orms, and polygenic autisms. Finally, the recent contributions of genome-wide association and whole exome sequencing studies will be highlighted.

Human RTEL1 deficiency causes Hoyeraal-Hreidarsson syndrome with short telomeres and genome instability.

Hoyeraal-Hreidarsson syndrome (HHS), a severe variant of dyskeratosis congenita (DC), is characterized by early onset bone marrow failure, immunodeficiency and developmental defects. Several factors involved in telomere length maintenance and/or protection are defective in HHS/DC, underlining the relationship between telomere dysfunction and these diseases. By combining whole-genome linkage analysis and exome sequencing, we identified compound heterozygous RTEL1 (regulator of telomere elongation helicase 1) mutations in three patients with HHS from two unrelated families. RTEL1 is a DNA helica…

Severe COVID-19 Unveils Atypical Familial Hemophagocytic Lymphohistiocytosis due to a Novel Homozygous PRF1 Variant.

We report a novel homozygous PRF1 variant, PRF1 (NM_001083116.3):c.343G > A (p.Glu115Lys), identified by whole-exome sequencing (WES) in an 11-year-old girl with atypical familial hemophagocytic lymphohistiocytosis (FHL). The variant, inherited from asymptomatic heterozygous parents, was absent or extremely rare in population databases and was predicted to be deleterious by multiple in silico tools. Born to consanguineous parents, the patient presented with recurrent fever, pancytopenia, and multiorgan failure following SARS-CoV-2 infection, further complicated by Epstein-Barr virus (EBV) and …

Genomics in psychiatric Nurse Practitioner practice: Moving from emerging trend to essential competency.

Genomics is increasingly influencing psychiatric practice as evidence links genetic variation with neurodevelopmental disorders, treatment response, and complex psychiatric presentations. Psychiatric nurse practitioners are well positioned to incorporate genomics into patient assessment and management; however, familiarity with testing options and clinical indications remains limited. This column reviews key genomic considerations for psychiatric practice, including pharmacogenomics, chromosomal microarray analysis, and exome or genome sequencing. Clinical "red flags," such as developmental de…

Successful Live Birth Following Treatment of Persistent Endometrial Dysbiosis and Recurrent Chronic Endometritis: A Case Report.

CASE: To study the cause of recurrent endometritis, which recurred after standard antibiotic therapy, we report the case of a 40-year-old woman with a history of recurrent pregnancy, preterm birth, and CE. The endometritis recurred following a standard antibiotic regimen. OUTCOME: Microbiome analysis via 16S rRNA gene sequencing revealed persistent dysbiosis in both vaginal and endometrial samples despite antibiotic regimens. Whole-exome sequencing (WES) identified rare variants in TRPV3 and CD36, potentially associated with epithelial barrier dysfunction. Following an extended course of anti…

Severe Ecthyma Gangrenosum in a Pediatric Patient With Neutropenia and a Novel HELLS Variant: Case Report.

Ecthyma gangrenosum (EG) is a rare and severe skin infection typically caused by Pseudomonas aeruginosa, often seen in immunocompromised pat … monas aeruginosa. He required multiple transfusions and fresh frozen plasma for coagulopathy. Whole-exome sequencing identified a novel HELLS variant (c.1904G>A; p.Cys635Tyr), classified as a variant of uncertain significance. This case underscores the diagnostic and management challenges of EG, highlighting the importance of early recognition and a mul …

IQ motif family genes in male infertility: pathogenesis, mechanisms, and clinical perspectives.

This review examines the critical role of IQ motif family genes in male infertility. Characterized by conserved calmodulin-binding IQ domain … rmia. The article discusses emerging diagnostic applications, including genetic screening via whole-exome sequencing and the evaluation of sperm protein biomarkers like IQCD. Furthermore, it outlines mechanism-informed therapeutic strategies, from clinically applied artificial oocyte activation for IQCN defects to preclinical explorations of gene correc …

Mandibular Distraction Osteogenesis in Monozygotic Twins With Structural-Dominant ALG8 Variants.

Biallelic ALG8 mutations typically manifest as lethal multisystem congenital disorders of glycosylation (CDG-Ih). We report a unique case of monozygotic female twins presenting with Pierre Robin sequence (PRS) and orofacial-digital (OFD)-like features (cleft lip, tongue hamartomas, digital anomalies) without classic metabolic crises. Whole-exome sequencing identified compound heterozygous variants (c.140C>T and c.1349+1G>A). Severe airway obstruction was successfully managed through bilateral mandibular distraction osteogenesis (MDO), achieving complete respiratory weaning and oral feeding. Th…

Long-term survival and molecular heterogeneity of sporadic multifocal non-functional pancreatic neuroendocrine tumors.

Multifocal sporadic non-functional pancreatic neuroendocrine tumors (NF-PanNETs) are rare, and their molecular underpinnings remain poorly understood. This study performed whole-exome sequencing on 35 synchronous primary tumors from 9 patients to characterize somatic alterations, copy-number variations, and clonal evolution. We found that multifocality was an independent risk factor for early recurrence. Significant intertumoral genomic heterogeneity was observed, with high discordance in both SNVs and CNVs between lesions. Enrichment of ATRX/MEN1 mutations in multifocal cases suggested a pote…

Прогрессивная слюнная речь как нетипичное представление GDAP2-относительно Spinocerebellar Ataxia: доклад по делу.

47-летний мужчина с сахарным диабетом и дислипидемией за четыре года развил прогрессивную речь. МРТ не выявила атрофии мозга, и обычные лабораторные и нейрофизиологические исследования были непримечательными. У его брата были похожие, но продвинутые симптомы, включая дисфагию и серьезные походки, что привело к зависимости от инвалидных колясок. Полноэкзомная последовательность выявила вероятную патогенную гомозиговую мутацию в гене GDAP2, подтверждающую диагноз атаксии 27 (SCAR27). В этом докладе подчеркивается важность рассмотрения наследственных атаксий при дифференциальном диагностике прогр

Совпадение в аннотации оригинала
A 47-year-old man with diabetes mellitus and dyslipidemia developed progressive slurred speech over four years. MRI revealed no cerebellar a … d symptoms, including dysphagia and severe gait impairment, leading to wheelchair dependence. Whole-exome sequencing identified a likely pathogenic homozygous nonsense mutation in the GDAP2 gene, confirming a diagnosis of autosomal recessive spinocerebellar ataxia type 27 (SCAR27). This report emphasizes the importance of considering hereditary ataxias …

Hydranencephaly Secondary to Placental Fetal Vascular Malperfusion in a Pregnancy with Extensive Uterine Fibromatosis.

INTRODUCTION: Hydranencephaly is a rare, destructive fetal brain disorder usually attributed to early bilateral carotid occlusion. CASE PRESENTATION: We report a 34-year-old primigravida with extensive uterine fibromatosis whose fetus showed normal neurosonography at 13 + 1 weeks, rapidly evolving to severe ventriculomegaly and near-complete supratentorial destruction by 18 weeks, with normal karyotype, array-CGH, and noncontributory exome sequencing. Postmortem examination confirmed classic hydranencephaly with preserved deep gray nuclei and a small cerebellum, while both carotid arteries we…

Neonatal hypocalcemia and hydrocephalus as early manifestations of intermediate osteopetrosis: successful hematopoietic stem cell transplantation despite negative genetic testing: a case report.

Osteopetrosis is a rare genetic skeletal disorder caused by defective osteoclast-mediated bone resorption, leading to increased bone density … ical findings supported the diagnosis of osteopetrosis, although targeted genetic testing and whole exome sequencing did not identify a causative variant. The patient was treated with calcium gluconate and vitamin D supplementation, followed by hematopoietic stem cell transplantation from an HLA-matched unrelated donor using peripheral blood stem cells. …

[Radiographic findings in a case of congenital generalized lipodystrophy].

Congenital generalized lipodystrophy (BerardinelliSeip syndrome) is a rare autosomal recessive disorder characterized by near-complete absen … ted the diagnosis of congenital generalized lipodystrophy. Despite normal leptin levels and a whole exome sequencing without pathogenic variants, the phenotype justifies clinical suspicion, suggesting the need for complementary genetic techniques to rule out large rearrangements. The association of facial dysmorphism, skin abnormalities, and craniofacia …

Preterm Finnish-type congenital nephrotic syndrome (NPHS1 variant) with multisystem involvement and TORCH coinfection.

This report describes a preterm male neonate who presented in his second month of life with seizures, anasarca and severe hypoalbuminaemia. Laboratory evaluation revealed heavy proteinuria, electrolyte disturbances and microbiological seropositivity (cytomegalovirus, herpes simplex virus, rubella), while urine culture isolated Klebsiella Whole-exome sequencing confirmed a homozygous NPHS1 variant consistent with Finnish-type congenital nephrotic syndrome. The infant required mechanical ventilation, inotropic support, daily albumin infusions, antiviral therapy and intensive electrolyte correcti…

Raw lacquer-associated familial chronic myelomonocytic leukemia with multi-hit TET2 mutations.

BACKGROUND: To explore the potential association between long-term exposure to raw lacquer and the development of chronic myelomonocytic leukemia (CMML). METHODS: We analyzed the clinical and hematological characteristics of an elderly couple with CMML. Whole-exome sequencing (WES) was performed to identify relevant gene variants, with a focus on TET2 mutation status. RESULTS: Two unrelated CMML patients within the same family, both with over 40 years of raw lacquer exposure, developed CMML. WES revealed that both patients harbored multi-hit TET2 gene mutations and lacked ASXL1 mutations. Bo…

Shared genomic features of HIV+ diffuse large B-cell lymphoma in two African cohorts.

The number of people with HIV (PWH) in Africa is rising due to population growth and antiretroviral therapy (ART) availability, with diffuse large B-cell lymphoma (DLBCL) a major cause of mortality. HIV and ART alter DLBCL tumor biology, but few studies of DLBCL include PWH or African patients, limiting translation of emerging treatment strategies. Here, we performed whole exome sequencing of 48 tumors (40 HIV-positive [HIV+]) with paired germline of DLBCL patients from Malawi and South Africa. HIV + DLBCL tumors had distinct mutations depending on ART exposure, and there were several recurren…

Biting off more than you can chew: a rare case of hyperparathyroidism jaw tumour syndrome.

Hyperparathyroidism Jaw Tumour Syndrome (HPT-JT) is a rare autosomal dominant disorder within the familial hyperparathyroidism group. Indivi … story of hyperparathyroidism and recent jaw tumour excision. Detailed family history prompted whole exome genetic testing which confirmed the presence of a pathogenic CDC73 gene mutation, ten years after the patient's initial parathyroidectomy. This case demonstrates the importance of detailed family history taking and the need to consider lesser-known …

Genetic and Clinical Characterization of Complex Glycerol Kinase Deficiency in Two Male Siblings: A Case Report.

Complex glycerol kinase deficiency (CGKD), also known as Xp21 contiguous gene deletion syndrome, is a rare X-linked recessive disorder resulting from partial deletion of the Xp21.3 chromosomal region. CGKD encompasses several loci, including glycerol kinase (GK), Duchenne muscular dystrophy (DMD), X-linked adrenal hypoplasia congenita (NR0B1), and intellectual developmental disorder (IL1RAPL1). We present the cases of two male siblings diagnosed with CGKD. The elder sibling was initially suspected of having congenital adrenal hypoplasia (CAH). Whole exome sequencing (WES) revealed an interstit…

Expanding the Clinical, Pathological, and Molecular Phenotypes of Tetratricopeptide 19 (TTC19) Gene Mutations: A Case Report from India.

Tetratricopeptide 19 gene (TTC19) is involved in mitochondrial respiratory chain (MRC) complex III function. Mutations cause developmental delay, Leigh syndrome, and spinocerebellar ataxia. In this report, we highlight the expanding phenotype of TTC19 gene variants. A 28-year-old man with intellectual disability presented with dysarthria, palatal tremors, and cerebellar ataxia of 5 months. After collecting clinical information and blood samples, clinical-exome sequencing was performed. Serum and cerebrospinal fluid lactate levels were elevated. Neuroimaging showed hypertrophic olivary degenera…

[Neonatal Diamond-Blackfan anemia: a case report].

A male full-term neonate was admitted at 30 minutes of life with pallor and 10 minutes of respiratory distress. Physical examination revealed pallor, increased intercanthal distance, low-set ears, a palpable cystic mass in the neck, hepatomegaly, a pedunculated, globular appendage attached to the right thumb, and an ectopic toenail on the right second toe. Laboratory testing showed severe anemia with hemoglobin of 44 g/L. Bone marrow examination demonstrated hypoplasia. Whole-exome sequencing identified a heterozygous pathogenic variant in the RPS19 gene, c.175T>C (p.Ser59Pro), establishing th…