Heterozygous missense variant in EIF6 gene: A novel form of Shwachman-Diamond syndrome?,American Journal of Medical Genetics Part A

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Heterozygous missense variant in EIF6 gene: A novel form of Shwachman-Diamond syndrome?
American Journal of Medical Genetics Part A ( IF 1.7 ) Pub Date : 2020-07-13 , DOI: 10.1002/ajmg.a.61758
Ai Ling Koh _{1,

2} , Carine Bonnard ₃ , Jiin Ying Lim _{1,

2} , Woei Kang Liew ₁ , Koh Cheng Thoon _{1,

2} , Terrence Thomas _{1,

2} , Nur Ain Binte Ali ₃ , Alvin Yu Jin Ng ₄ , Sumanty Tohari ₄ , Kong Boo Phua _{1,

2} , Byrappa Venkatesh _{4,

5} , Bruno Reversade _{3,

4,

5} , Saumya Shekhar Jamuar _{1,

2,

6,

7}

Affiliation

Shwachman–Diamond syndrome (SDS) is a rare multisystem ribosomal biogenesis disorder characterized by exocrine pancreatic insufficiency, hematologic abnormalities and bony abnormalities. About 90% of patients have biallelic mutations in SBDS gene. Three additional genes—EFL1, DNAJC21 and SRP54 have been reported in association with a SDS phenotype. However, the cause remains unknown for ~10% of patients. Herein, we report a 6‐year‐old Chinese boy, who presented in the neonatal period with pancytopenia, liver transaminitis with hepatosplenomegaly and developmental delay, and subsequently developed pancreatic insufficiency complicated by malabsorption and poor growth. Exome sequencing identified a novel de novo heterozygous variant in EIF6 (c.182G>T, p.Arg61Leu). EIF6 protein inhibits ribosomal maturation and is removed in the late steps of ribosomal maturation by SBDS and EFL1 protein. Given the interaction of EIF6 with SBDS and EFL1, we postulate heterozygous variants in EIF6 as a novel cause of Shwachman–Diamond‐like phenotype. We compared the phenotype of our patient with those in patients with mutation in SBDS, EFL1, DNAJC21, and SRP54 genes to support this association. Identification of more cases of this novel phenotype would strengthen the association with the genetic etiology.

更新日期：2020-08-15

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