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Expanding the phenotypic and mutational spectrum in microcephalic osteodysplastic primordial dwarfism type I
Ghada M H Abdel-Salam1, Mohamed S Abdel-Hamid, Mahmoud Issa
1Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt. ghada.abdelsalam@yahoo.com
Abstract:
Mutations in the RNU4ATAC gene cause microcephalic osteodysplastic primordial dwarfism type I. It encodes U4atac, a small nuclear RNA that is a component of the minor spliceosome. Six distinct mutations in 30 patients diagnosed as microcephalic osteodysplastic primordial dwarfism type I have been described. We report on three additional patients from two unrelated families presenting with a milder phenotype of microcephalic osteodysplastic primordial dwarfism type I and metopic synostosis. Patient 1 had two novel heterozygous mutations in the 3' prime stem-loop, g.66G > C and g.124G > A while Patients 2 and 3 had a homozygous mutation g.55G > A in the 5' prime stem-loop. Although they manifested the known spectrum of clinical features of microcephalic osteodysplastic primordial dwarfism type I, they lacked evidence of severe developmental delay and neurological symptoms. These findings expand the mutational and phenotypic spectrum of this syndrome.
Insights
Mutations in the RNU4ATAC gene cause microcephalic osteodysplastic primordial dwarfism type I. New research identifies novel mutations and a milder phenotype, expanding the syndrome
Area of Science:
- Genetics
- Molecular Biology
- Developmental Biology
Background:
- Microcephalic osteodysplastic primordial dwarfism type I (MOPD I) is a rare genetic disorder.
- It is caused by mutations in the RNU4ATAC gene, which encodes a component of the minor spliceosome.
- Previous studies identified six distinct mutations in 30 MOPD I patients.
Observation:
- This study reports on three additional patients from two families with a milder MOPD I phenotype.
- These patients also presented with metopic synostosis.
- Genetic analysis revealed novel heterozygous mutations (g.66G > C, g.124G > A) and a homozygous mutation (g.55G > A) in the RNU4ATAC gene.
Findings:
- The identified mutations expand the known mutational spectrum of RNU4ATAC.
- Patients exhibited clinical features of MOPD I but lacked severe developmental delay and neurological symptoms.
- This suggests a milder phenotypic presentation associated with these specific mutations.
Implications:
- These findings broaden the understanding of MOPD I's genetic and clinical variability.
- The study highlights the importance of genetic testing for RNU4ATAC mutations in patients with primordial dwarfism.
- Further research may elucidate genotype-phenotype correlations and inform clinical management.
