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Case Reports
. 2022 May;188(5):1595-1599.
doi: 10.1002/ajmg.a.62681. Epub 2022 Feb 5.

Further delineation of SET-related intellectual disability syndrome

Kenta Shono  1 , Yumi Enomoto  2 , Yoshinori Tsurusaki  2 , Tatsuro Kumaki  1 , Mitsuo Masuno  3 , Kenji Kurosawa  1
Affiliations
Case Reports

Further delineation of SET-related intellectual disability syndrome

Kenta Shono et al. Am J Med Genet A. 2022 May.

Abstract

A loss-of-function mutation of SET causes nonsyndromic intellectual disability, often associated with mild facial dysmorphic features, including plagiocephaly, facial asymmetry, broad and high forehead, a wide mouth, and a prominent mandible. We report a male individual with a 2.0 Mb deletion within 9q34.11, involving SET and SPTAN1, but not STXBP1. Among the genes with a high probability of being loss-of-function intolerant in the deletion interval, only SPTAN1 and SET had haploinsufficiency score (%HI) <10, indicating a high likelihood of haploinsufficiency. Pathogenic variants in SPTAN1 are responsible for early-onset epileptic encephalopathy by exerting a dominant-negative effect. However, whether haploinsufficiency of SPTAN1 alone also causes the severe phenotype remained unknown. SET is a regulator of cell differentiation in early human development and a component of the inhibitor of histone acetyltransferases complex. Therefore, combining the previously reported patients, our patient delineated the phenotypic spectrum of SET-related nonsyndromic intellectual disability with mild facial dysmorphism.

Keywords: 9q34.11; SET; SPTAN1; haploinsufficiency; nonsyndromic intellectual disability.

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References

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