Scholarlink

Background <p>This study aimed to identify <i>GBA1</i> variants in Egyptian Gaucher disease (GD) patients residing in a region with high consanguinity and to correlate these genotypes with their clinical phenotypes.</p> Methodology <p>This descriptive study included 68 Egyptian patients diagnosed with GD. Diagnosis relied upon reduced β-glucocerebrosidase activity measured by tandem mass spectrometry from dried blood spots and confirmed by <i>GBA1</i> single-gene sequencing. Clinical and laboratory information were gathered from patient records, and neurological evaluations were conducted by a neurologist.</p> Results <p>Thirty patients (44.1%) were classified as type 1 GD, three (4.4%) as type 2 GD, and 35 patients (51.5%) as type 3 GD. Variant analysis of the 136 alleles identified 19 different variants. The most prevalent mutant allele was c.1448T &gt; C p.(Leu483Pro) (50.7%). Seven novel variants were documented: five homozygous missense variants, including c.263&#xa0;C &gt; T p.(Met88Thr), c.1331&#xa0;A &gt; G p.(Asp444Gly), c.1409&#xa0;C &gt; T p.(Ser470Phe), c.907&#xa0;C &gt; G p.(Leu303Val), c.1574G &gt; A p.(Gly525Asp), two heterozygous missense variants: c.380&#xa0;C &gt; G p.(Ala127Gly) and c.453 + 2T &gt; C. All carriers of these novel variants were phenotypically classified as type 1 GD. Genotype–phenotype correlations confirmed that the c.1226&#xa0;A &gt; G p.(Asn409Ser) variant was confined to type 1 GD, whereas c.1448T &gt; C p.(Leu483Pro) was associated with types 2 and 3 GD.</p> Conclusion <p>Variant analysis of 136 alleles identified 19 <i>GBA1</i> variants, including seven novel variants. These findings enhance genotype–phenotype correlations, provide genetic counseling, and enable customized molecular analyses for families at risk.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Acid β-glucosidase (GBA1) gene mutational spectrum and clinical phenotypes in patients with gaucher disease: seven novel mutations in a multicenter retrospective cohort study from upper Egypt

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月1日

查看全文
  • Mervat A. M. Youssef,
  • Solaf M. Elsayed,
  • Khalid I. Elsayh,
  • Sherin A. Taha,
  • Hala S.M. Abdelmotogaly,
  • Mostafa M. Embaby

摘要

Background

This study aimed to identify GBA1 variants in Egyptian Gaucher disease (GD) patients residing in a region with high consanguinity and to correlate these genotypes with their clinical phenotypes.

Methodology

This descriptive study included 68 Egyptian patients diagnosed with GD. Diagnosis relied upon reduced β-glucocerebrosidase activity measured by tandem mass spectrometry from dried blood spots and confirmed by GBA1 single-gene sequencing. Clinical and laboratory information were gathered from patient records, and neurological evaluations were conducted by a neurologist.

Results

Thirty patients (44.1%) were classified as type 1 GD, three (4.4%) as type 2 GD, and 35 patients (51.5%) as type 3 GD. Variant analysis of the 136 alleles identified 19 different variants. The most prevalent mutant allele was c.1448T > C p.(Leu483Pro) (50.7%). Seven novel variants were documented: five homozygous missense variants, including c.263 C > T p.(Met88Thr), c.1331 A > G p.(Asp444Gly), c.1409 C > T p.(Ser470Phe), c.907 C > G p.(Leu303Val), c.1574G > A p.(Gly525Asp), two heterozygous missense variants: c.380 C > G p.(Ala127Gly) and c.453 + 2T > C. All carriers of these novel variants were phenotypically classified as type 1 GD. Genotype–phenotype correlations confirmed that the c.1226 A > G p.(Asn409Ser) variant was confined to type 1 GD, whereas c.1448T > C p.(Leu483Pro) was associated with types 2 and 3 GD.

Conclusion

Variant analysis of 136 alleles identified 19 GBA1 variants, including seven novel variants. These findings enhance genotype–phenotype correlations, provide genetic counseling, and enable customized molecular analyses for families at risk.