Two mutations in the SBDS gene reveal a diagnosis of Shwachman-Diamond syndrome in a patient with atypical symptoms.

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor Molecular Case Studies Pub Date : 2022-12-28 Print Date: 2022-12-01 DOI:10.1101/mcs.a006237
María Noel Spangenberg, Sofia Grille, Camila Simoes, Nicolás Dell'Oca, Matilde Boada, Cecilia Guillermo, Victor Raggio, Lucía Spangenberg
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Abstract

We present the case of a 53-yr-old woman with an inherited bone marrow failure coexisting with uncommon extrahematological symptoms, such as cirrhosis and skin abnormalities. Whole-exome sequencing revealed a diagnosis of Shwachman-Diamond syndrome (SDS) with an atypical presentation. Unexpected was the age of disease expression, normally around the pediatric age, with a predominantly median survival age of 36 yr. To our knowledge, she was the first adult patient with a molecular diagnosis of Shwachman-Diamond in Uruguay. The patient was referred to our service when she was 43-yr-old with a history of bone marrow failure with anemia and thrombocytopenia. All secondary causes of pancytopenia were excluded. Bone marrow aspirate and biopsy specimens were hypocellular for the patient's age. Numerous dysplastic features were observed in the three lineages. She had a normal karyotype and normal chromosomal fragility. A diagnosis of low-risk hypoplastic MDS was made. Dermatological examination revealed reticulate skin pigmentation with hypopigmented macules involving the face, neck, and extremities; nail dystrophy; premature graying; and thin hair. Extrahematological manifestations were present (e.g., learning difficulties, short stature). Last, she was diagnosed with cryptogenic liver cirrhosis CHILD C. This rules out all other possible causes of chronic liver disease. This clinical presentation initially oriented the diagnosis toward telomeropathy, so we did a telomeropathy NGS panel that came up negative. Finally, we did an exome sequencing that confirmed the diagnosis of SDS. Using whole-exome sequencing, we were able to find two compound heterozygous mutations in the SBDS gene that were responsible for the phenotype of a patient that was undiagnosed for 10 years. An earlier genetic diagnosis could have influenced our patient's outcome.

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SBDS 基因的两个突变揭示了一名非典型症状患者的 Shwachman-Diamond 综合征诊断。
我们报告了一例 53 岁女性患者的病例,她患有遗传性骨髓衰竭,同时伴有肝硬化和皮肤异常等不常见的血液学外症状。全外显子组测序结果显示,患者被诊断为舒瓦赫曼-钻石综合征(SDS),且表现不典型。据我们所知,她是乌拉圭第一例经分子诊断患有舒瓦赫曼-钻石综合征的成年患者。患者在 43 岁时因贫血和血小板减少的骨髓衰竭病史被转诊到我们的服务部门。所有继发性全血细胞减少症的病因均被排除。骨髓穿刺和活检标本与患者的年龄不符,呈低细胞状态。在三个系中观察到许多发育不良的特征。她的核型正常,染色体脆性正常。诊断结果为低风险低增生性骨髓增生异常综合症。皮肤科检查发现,她的皮肤色素沉着呈网状,面部、颈部和四肢有色素沉着斑;指甲萎缩;早白;头发稀疏。此外,她还出现了血液学以外的表现(如学习困难、身材矮小)。最后,她被诊断为隐源性肝硬化 CHILD C。这种临床表现最初将诊断方向锁定在端粒病上,因此我们做了端粒病NGS检测,结果呈阴性。最后,我们进行了外显子组测序,确诊为 SDS。通过全外显子组测序,我们在 SBDS 基因中发现了两个复合杂合突变,这两个突变是导致患者表型的原因,而该患者在 10 年中一直未被确诊。更早的基因诊断可能会影响患者的预后。
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来源期刊
Cold Spring Harbor Molecular Case Studies
Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.20
自引率
0.00%
发文量
54
期刊介绍: Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.
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