A novel variant in GNPNAT1 gene causing a spondylo-epi-metaphyseal dysplasia resembling PGM3—Desbuquois like dysplasia

Rasha Moheb Elhossini*, Hoda Abdalla Ahmed, Ghada Otaify, Raghda M. Ghorab, Khalda Amr, Mona Aglan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Spondylo-epi-metaphyseal dysplasias (SEMDs) are a clinically and genetically heterogeneous group of skeletal dysplasias characterized by short stature and abnormal modeling of the spine and long bones. A novel form of rhizomelic skeletal dysplasia, Ain-Naz type, associated with a homozygous variant in GNPNAT1 was recently identified. Herein, we report an Egyptian patient, offspring of consanguineous parents, who presented with a severe form of unclassified SEMD. Whole exome sequencing identified a novel homozygous variant in exon 3, c.77T>G, (p.Phe26Cys) in GNPNAT1, that was confirmed by Sanger sequencing and both parents were found to be heterozygous for the identified variant. Main features included severe short stature, rhizomelic limb shortening, and wide flared metaphysis. Short broad long bones, brachydactyly, delayed epiphyseal ossification of long bones, advanced bone age, and immunodeficiency were additional findings expanding the clinical phenotype described in the previously reported family. We conclude that variants in the GNPNAT1 gene cause an autosomal recessive form of SEMD resembling Desbuquois like dysplasia caused by PGM3, which is involved in the same pathway as GNPNAT1.

Original languageEnglish
Pages (from-to)2861-2868
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Issue number10
Publication statusPublished - Oct 2022
Externally publishedYes


  • PGM3
  • SEMD
  • whole exome sequencing

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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