Latest Genetics (clinical) research

Top 10 this week

Week of 1 November 2026

1. 1

   Diagnostic Yield and Clinical Actionability of Genetic Testing in Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis

   International journal of molecular sciences · Q1 journal · SR of cohorts · Evidence level 2 (Moderate) · 14 October 2026

   Across 7,641 patients, genetic testing identified a cause in 28%; yield varied by test, from 16% with chromosomal microarray to 43% with whole-genome sequencing. Among patients with a confirmed diagnosis, findings were considered clinically actionable in 58%, but substantial differences across studies and very low certainty of evidence leave the expected benefit for individual patients unclear.

2. 2

   Genotype, Phenotypic Severity, and Survival in Pediatric Dilated Cardiomyopathy: A Report From the Pediatric Cardiomyopathy Registry

   Circulation. Heart failure · Q1 journal · Prospective cohort · Evidence level 2 (Moderate) · 27 October 2026

   In a 279-child study, testing found a disease-associated gene variant in 19%, with higher detection among children diagnosed after age 12. A genetic finding did not track with heart failure symptoms, heart ultrasound severity, or death or transplant; those outcomes were similarly poor, while heart function tended to normalize more often without an identified variant.

3. 3

   Germline BRCA-Lynch syndrome MINAS: report of six Argentinian families and a systematic review of the literature

   Familial cancer · Q2 journal · SR of cohorts · Evidence level 2 (Moderate) · 28 October 2026

   Across six newly reported families and published cases, cancer patterns were balanced between BRCA-related and Lynch syndrome tumors, while cancers outside those patterns were uncommon. Carriers with MLH1 or MSH2/EPCAM variants more often had multiple tumors and cancers outside the colon than those with MSH6 or PMS2 variants; whether the syndromes interact remains unclear because patients were clinically selected.

4. 4

   Recurrent Acute Liver Failure in Children: A Systematic Review of Genetic Etiologies, Diagnostic Clues, and Liver Transplantation

   Genes · Q2 journal · SR of cohorts · Evidence level 2 (Moderate) · 2 October 2026

   This review retained 44 publications covering 41 study or cohort units on recurrent acute liver failure in children, but evidence was mostly case reports, small series, and retrospective cohorts. The authors propose genomic testing during a first unexplained severe episode rather than waiting for recurrence; treatment and transplant guidance remains uncertain because data are limited.

5. 5

   Diagnostic Yield and Clinical Phenotype in a Lithuanian Familial Hypercholesterolemia Cohort with Heterogeneous Sequencing Platforms

   Medicina (Kaunas, Lithuania) · Q2 journal · Prospective cohort · Evidence level 2 (Moderate) · 29 September 2026

   In this single-center Lithuanian cohort, 13 of 48 adults had a pathogenic variant in LDLR or APOB; those with LDLR variants had higher cholesterol levels than those without a detected pathogenic variant. The historical tests varied in scope, so a negative result does not rule out FH, and the study could not determine whether pharmacogenomic findings predict statin response or intolerance.

6. 6

   Early Amniocentesis Versus Transabdominal Chorionic Villus Sampling for Early Invasive Prenatal Diagnosis: A 15-Year Prospective Cohort Study

   Genes · Q2 journal · Prospective cohort · Evidence level 2 (Moderate) · 26 September 2026

   In 3,238 singleton pregnancies, early amniocentesis and transabdominal chorionic villus sampling produced chromosome results in 99.9% and 99.8% of cases, respectively. Pregnancy loss was rare and did not differ between methods; targeted testing also found pathogenic genetic changes in 5 of 35 fetuses with structural abnormalities. The comparison comes from one operator, so results may not reflect every setting.

7. 7

   From Fragmentation to Standardization: A Systematic Review Update and Critical Appraisal of Genetic and Genomic Testing Assessment Frameworks and Their Alignment With the HTA Core Model

   Health science reports · Q2 journal · SR of cohorts · Evidence level 2 (Moderate) · 28 October 2026

   A review of 24 frameworks found most were fragmented or incomplete; the HTA Core Model covered all core questions and every assessment component identified, though coverage varied. It could provide a common basis for evaluating genetic and genomic tests, but genomic-specific additions and validation are still needed before it can standardize practice.

8. 8

   Exploring genetic variants in premature ovarian insufficiency: a cohort-based investigation of monogenic etiologies

   Journal of the Endocrine Society · Q2 journal · Prospective cohort · Evidence level 2 (Moderate) · 28 October 2026

   In 160 women, genetic testing found pathogenic or likely pathogenic variants in 19.3%, but only 7.5% were relevant after accounting for gene evidence and inheritance; focusing on the 40 best-supported genes yielded a 4.4% diagnostic rate. Yield reached 15.4% among women with primary amenorrhea, underscoring that most cases remain unexplained by current panels.

9. 9

   Effect of implementation of a clinical checklist on the evaluation of constitutional mismatch repair deficiency in a neurofibromatosis clinic

   Journal of community genetics · Q2 journal · Prospective cohort · Evidence level 2 (Moderate) · 30 October 2026

   After checklist implementation, ambiguous responses fell, more patients met criteria for constitutional mismatch repair deficiency evaluation, and genetic referrals were more frequent than before. However, meeting evaluation criteria did not correlate with referral in either study phase, so the checklist did not ensure follow-up. Children with a nondiagnostic neurofibromatosis type 1 workup who meet criteria still need further evaluation.

10. 10

    Molecular Biomarkers and Pathways in Recurrent Spontaneous Abortion: A Systematic Review

    International journal of fertility & sterility · Q2 journal · SR of cohorts · Evidence level 2 (Moderate) · 3 October 2026

    A review of nine studies found chromosomal abnormalities in nearly half of first-trimester recurrent losses, while variants in genes including NLRP7, KHDC3L and VEGF were also linked to risk. These findings offer clues to how pregnancy loss may occur, but the evidence comes largely from small, single-population studies; broader validation is needed before biomarkers can guide routine care.

Paper of the day, last two weeks

• Evaluating Genomic Testing in Pediatric Inborn Errors of Immunity: An Optimal Model of Care

  Journal of clinical immunology · Q1 journal · Unclassified · Evidence level 5 (Expert Opinion) · 6 August 2026

  Genomic diagnostic yield and care-model outcomes in pediatric immunodeficiency

• Genomic ascertainment refines the population prevalence and phenotype associations of germline TERT variants

  PLoS genetics · Q1 journal · Case-control · Evidence level 3 (Low) · 5 November 2026

  In two large genomic cohorts, deleterious variants in one copy of the telomerase gene occurred in about 1 in 1,200 to 1 in 2,300 people. Pulmonary fibrosis was six to eleven times more common in carriers in both cohorts, while liver disease and head and neck cancer associations appeared in only one; cohort differences may explain the uneven findings.

• Genetic testing considerations for hereditary duodenopancreatic neuroendocrine tumors

  Journal of neuroendocrinology · Q1 journal · Cohort · Evidence level 4 (Very Low) · 1 November 2026

  Among 410 patients tested for duodenal or pancreatic neuroendocrine tumors, disease-linked variants were found in 29% of those with a hereditary syndrome, compared with fewer than 2% of those with isolated tumors; most were in MEN1. The authors support testing guided by clinical signs and suggest broader MEN1 testing for isolated cases with gastrinoma, multiple tumors, or diagnosis before age 40.

• Childhood-onset hereditary spastic paraplegia: at the crossroads between neurodevelopment and neurodegeneration

  European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society · Q1 journal · Retrospective cohort · Evidence level 3 (Low) · 29 October 2026

  In a Spanish cohort of 91 children with hereditary spastic paraplegia, genetic testing identified a cause in 62%; 58% of the variants were in genes not classically linked to the condition. Developmental delay and gait problems were common, and more than half had complex symptoms. The findings underscore the need for broader genetic testing and better tools to track childhood disease.

• Germline Genetic Variants and Epilepsy Surgery Response: Individual Participant Pooled Analysis of 272 Patients

  Neurology · Q1 journal · SR of cohorts · Evidence level 2 (Moderate) · 2 November 2026

  In a pooled analysis of 272 people with germline genetic epilepsies, seizure freedom after resection or laser ablation varied by genetic pathway: rates were highest for GATORopathies and vascular disorders, and lowest for synaptopathies and channelopathies. Even when MRI showed a lesion, outcomes remained lower for the latter groups; prospective studies are needed to guide surgical selection.

• Expanded Carrier Screening in gamete donation identifies clinically relevant donor-recipient genetic incompatibilities

  Journal of assisted reproduction and genetics · Q1 journal · Retrospective cohort · Evidence level 3 (Low) · 29 October 2026

  In this retrospective cohort of 250 couples using donor-assisted fertility treatment, expanded carrier screening identified shared carrier findings in 26% to 44% of those matched using the test. The findings do not all represent clinically meaningful risks: added value beyond standard donor screening depends on the condition and which genes and variants were already assessed, requiring gene-level data to clarify its benefit.

• Whole-exome sequencing in a Turkish autism spectrum disorder cohort: a retrospective study of molecular diagnostic yield in isolated and complex presentations

  BMC psychiatry · Q1 journal · Retrospective cohort · Evidence level 4 (Very Low) · 13 October 2026

  Large cohort quantifies exome diagnostic yield by clinical presentation

• Efficiency of Rapid Whole-Genome Sequencing in Pediatric Intensive Care Units: Experience in a Diverse Population

  International journal of molecular sciences · Q1 journal · Unclassified · Evidence level 5 (Expert Opinion) · 19 October 2026

  Across four centers in diverse New Jersey, rapid whole-genome sequencing identified a cause in 19 of 52 infants and children tested, and most positive results informed treatment, care decisions, or genetic counseling. Unexplained failure to thrive had the highest diagnostic yield, but the small study does not establish which children benefit most from testing.

• Genetic analysis of fetal corpus callosum abnormalities: a retrospective single-center cohort study

  The Journal of molecular diagnostics : JMD · Q1 journal · Retrospective cohort · Evidence level 4 (Very Low) · 27 October 2026

  In this single-center study of 86 fetuses with corpus callosum abnormalities, chromosomal testing found a diagnosis in 13.9%; exome sequencing added diagnoses in 26.9% of tested cases with negative chromosomal results. Detection was highest among fetuses with multiple organ-system anomalies, but that difference was not statistically significant, so larger studies are needed to guide testing.

• Low Incidence of Cryptic Genetic Marrow Failure in Pediatric Severe Aplastic Anemia Following Negative Clinical Workup

  Blood · Q1 journal · Cohort · Evidence level 3 (Low) · 28 October 2026

  Among 113 children with severe aplastic anemia and no clinical or laboratory signs of inherited marrow failure, enhanced genetic testing found no diagnostic variants. Two of 36 children with suggestive findings had potentially relevant variants, though one case remained unresolved. The retrospective results suggest treatment need not wait for genetic testing after a comprehensive negative workup, but broader evidence is needed.

• Loss-of-function variants in CFAP57, SEPTIN4, SPEM2, and CFAP46 cause asthenoteratozoospermia

  Human reproduction (Oxford, England) · Q1 journal · Unclassified · Evidence level 5 (Expert Opinion) · 21 October 2026

  Sequencing in 13 consanguineous families identified loss-of-function variants in CFAP46, CFAP57, SEPTIN4 and SPEM2 linked to asthenoteratozoospermia. Mouse experiments showed CFAP46 is needed for sperm flagella assembly and head remodeling, while unresolved cases carried more rare damaging variants than fertile controls. Whether these variant combinations directly contribute to infertility still needs functional testing.

• Screening of fabry disease in patients with left ventricular hypertrophy: a single-center study in Mexico

  Orphanet journal of rare diseases · Q1 journal · Unclassified · Evidence level 5 (Expert Opinion) · 25 July 2026

  In this single-center Mexican study, genetic testing identified Fabry disease in three of 205 patients with unexplained left ventricular hypertrophy (1.5%); cascade screening then found three more affected women. The findings support considering genetic testing in women with this heart finding, but the small referral-center sample and uncertain genotype-phenotype links limit what can be concluded about prevalence and treatment.

• Polygenic risk score identifies alternative etiologies in misdiagnosed cases of primary adrenal insufficiency

  The Journal of clinical investigation · Q1 journal · Unclassified · Evidence level 5 (Expert Opinion) · 22 October 2026

  Genomic reevaluation uncovers monogenic causes of adrenal insufficiency

Evidence summaries in Genetics (clinical)

• Urea Cycle Disorders
• Neural Crest Cell Migration