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Case Reports
. 2022 Jul;188(7):1972-1978.
doi: 10.1002/ajmg.a.62723. Epub 2022 Mar 11.

A new missense variant in RAB3GAP2 in a family with muscular dystrophy-short stature and defective autophagy: An expansion of the micro/Martsolf spectrum or a new phenotype?

German A Mora-Roldan  1   2 , Carlos Galaviz-Hernandez  3 , Jose Hiebert-Froese  4 , Arturo Hernandez  5   6 , Luis Montes  1 , Maria L Duran-Pasten  6 , Karlen Gazarian  2 , Juan C Zenteno  1   7
Affiliations
Case Reports

A new missense variant in RAB3GAP2 in a family with muscular dystrophy-short stature and defective autophagy: An expansion of the micro/Martsolf spectrum or a new phenotype?

German A Mora-Roldan et al. Am J Med Genet A. 2022 Jul.

Abstract

We describe a sibling pair of Mennonite origin born from consanguineous parentage with a likely new phenotype of limb-girdle muscular dystrophy, short stature, ptosis, and tracheomalacia. Exome sequencing in the affected subjects identified a novel homozygous RAB3GAP2 missense variant as the potential causal variant. As RAB3GAP2 has been recently shown to be involved in the autophagy process, we analyzed patient-derived fibroblasts by fluorescence microscopy and demonstrated defective autophagic flux under rapamycin and serum starvation conditions when compared with wild-type cells. The phenotype in the siblings described here is distinct from Martsolf and Warburg's micro syndromes, the currently known diseases arising from RAB3GAP2 pathogenic variants. Thus, this work describes a potentially novel recessive phenotype associated with a RAB3GAP2 defect and manifesting as a muscular dystrophy-short stature disorder with no ocular anomalies. Functional analyses indicated defective autophagy in patient-derived fibroblasts, supporting the involvement of RAB3GAP2 in the etiology of this disorder. Our results contribute to a better characterization of the Martsolf/micro spectrum phenotype.

Keywords: RAB3GAP2; autophagy; muscular dystrophy.

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References

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