{"id":273,"title":"Case Report: Familial TBX4-related developmental lung disease: two siblings with fatal neonatal respiratory failure","title_zh":"家族性TBX4相关发育性肺疾病：两同胞致死性新生儿呼吸衰竭病例报告","url":"https://pubmed.ncbi.nlm.nih.gov/42991514","doi":"10.3389/fped.2026.1816836","pmid":"42991514","journal":"Front Pediatr","kind":"paper","lang":"en","published_at":"2026-10-22T00:00:00+00:00","fetched_at":"2026-11-08T03:44:04+00:00","authors":["Thiruvenkataramani RP","Mohamed T","Pugmire MV","Omar SA"],"primary_topic":"pgt","topics":[{"slug":"pgt","score":1.0,"hits":["preimplantation genetic"]},{"slug":"repro-genetics","score":1.0,"hits":["whole-exome"]}],"topic_score":1.0,"preference_score":0.0,"preference_labels":[],"llm_score":66.0,"final_score":66.0,"score_dims":{"novelty":65,"rigor":55,"impact":55,"relevance":75,"translation":68},"recommend_reason":"病例少但表型与遗传学证据完整，且直接涉及PGT胚胎携带率，对生殖遗传咨询和PGT决策有参考价值；作为个案报告证据等级有限，适合浏览而非必读。","keywords":["TBX4","发育性肺疾病","新生儿呼吸衰竭","全外显子测序","植入前遗传学检测","肺动脉高压"],"selected":1,"story_id":338,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-endo-genetics","source_name":"PubMed · 生殖内分泌/遗传/保存","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":null,"journal_tier":"standard","journal_if":null,"is_mock":false,"summary_zh":"该病例报告描述两例同胞新生儿致死性呼吸衰竭：足月女婴生后11小时死亡，晚期早产男婴生后9小时死亡，均表现为严重低氧血症和肺动脉高压，尸检提示肺发育不良。全外显子测序发现来自无症状父亲的杂合TBX4变异c.741G>C（p.Lys247Asn），10枚胚胎中7枚检出该变异。结论提示TBX4相关发育性肺疾病谱可扩展，对不明原因新生儿呼吸衰竭及肺动脉高压应考虑TBX4检测。","summary":"BACKGROUND: T-box transcription factor 4 (TBX4) is a critical regulator of lung and pulmonary vascular development. Pathogenic TBX4 variants are associated with developmental lung disease, pulmonary hypertension, and neonatal respiratory failure. CASE PRESENTATION: We report two siblings with lethal neonatal respiratory failure. The first, a term female infant, died at 11 h of life, and her late-preterm male sibling died at 9 h despite maximal intensive care. Both developed severe hypoxemia and pulmonary hypertension. Autopsy demonstrated marked pulmonary hypoplasia. Whole-exome sequencing identified a novel heterozygous TBX4 variant, c.741G>C (p.Lys247Asn), inherited from their unaffected father. Preimplantation genetic testing detected the variant in seven of 10 embryos. CONCLUSION: These cases expand the spectrum of TBX4-associated developmental lung disease and support consideration of TBX4 testing in neonates with unexplained respiratory failure and pulmonary hypertension.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}