A novel frameshift pathogenic variant in ST3GAL5 causing salt and pepper developmental regression syndrome (SPDRS): A case report

Jamal Manoochehri,Seyed Mohammad Bagher Tabei,Sanaz Mohammadi,Zahra Sharifi,Seyed Alireza Dastgheib,Maryam Mollaie,Fatemeh Dehghanian,Hossein Jafari Khamirani,Zahra Farbod,Mehdi Dianatpour,Sina Zoghi

doi:10.1038/s41439-021-00164-8

Jamal Manoochehri, Seyed Mohammad Bagher Tabei + Show 9 more

Open Access

https://doi.org/10.1038/s41439-021-00164-8

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Abstract

GM3 synthase deficiency is associated with salt and pepper developmental regression syndrome (SPDRS), a rare genetic disorder. Herein, we report the first Iranian patient with SPDRS. We detected a novel pathogenic variant of ST3GAL5 (NM_003896.4: c.1030_1031del, p.Ile344Cysfs*11). The proband had intellectual disability (ID), failure to thrive, cerebral atrophy, microcephaly, and atonic seizures. The main future challenge proceeding from the results of this study is the prenatal detection of the newly discovered variant; the next step would involve further studies to elucidate the phenotypic spectrum of SPDRS and detect new variants that could cause symptoms ranging from mild to severe.

Highlights

GM3 synthase is the first enzyme involved in the biosynthesis of aand b-series gangliosides
We report the clinical features of the first Iranian patient with salt and pepper developmental regression syndrome (SPDRS); in this case, the disease was caused by a novel pathogenic variant (NM_003896.4: c.1030_1031del, p.Ile344Cysfs*11) of ST3GAL5
This report is written in compliance with the CAse REport (CARE) Statement[3]

Summary

Jamal Seyed

Manoochehri[1,2], Seyed Alireza Dastgheib[3], Hossein Mohammad Bagher Tabei[3,5], Sanaz Mohammadi[2], FJaatfeamri eKhhaDmehirganhiania2,n3,2,MZaarhyraamFaMrboolldai2e4a,nZdahMreahSdhiaDriifia4n,aStipnoauZr3o,6g✉hi[4],. We report the clinical features of the first Iranian patient with SPDRS; in this case, the disease was caused by a novel pathogenic variant (NM_003896.4: c.1030_1031del, p.Ile344Cysfs*11) of ST3GAL5. The proband was a three-and-a-half-year-old girl who was referred to our center with global developmental delay She was the only child born to consanguineous parents (Fig. 1A). The patient’s low weight, poor weight gain, and microcephaly suggested failure to thrive (classified as severe by the Gomez criteria) She had severe ID, in line with previous reports of SPDRS. No language development was apparent, and the patient remained mute with poor nonverbal expression She had experienced mild atonic seizures a year earlier. WES identified a homozygous frameshift pathogenic variant (NM_003896.4: c.1030_1031del, p.Ile344Cysfs*11) of ST3GAL5 in the proband; this variant was found in both parents in a heterozygous state.

Human Genome Variation

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