2. Academic Validation
  3. Biallelic novel missense HHAT variant causes syndromic microcephaly and cerebellar-vermis hypoplasia

Biallelic novel missense HHAT variant causes syndromic microcephaly and cerebellar-vermis hypoplasia

  • Am J Med Genet A. 2019 Jun;179(6):1053-1057. doi: 10.1002/ajmg.a.61133.
Ghada M H Abdel-Salam 1,  Inas Mazen 1,  Maha Eid 2,  Nour Ewida 3,  Ranad Shaheen 3,  Fowzan S Alkuraya 3 4 5
Affiliations

Affiliations

  • 1 Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
  • 2 Human Cytogenetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
  • 3 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • 4 Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
  • 5 Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
PMID: 30912300 DOI: 10.1002/ajmg.a.61133
Abstract

We report two siblings with microcephaly, early infantile onset seizures, and cerebellar vermis hypoplasia, in whom whole exome sequencing revealed a novel homozygous missense (c.770T>C, p.[Leu257Pro]) variant in the Hedgehog acyl-transferase gene (HHAT), encoding an Enzyme required for the attachment of palmitoyl residues that are critical for multimerization and long and short range Hedgehog signaling. There is a report of one family with Nivelon-Nivelon-Mabille syndrome in which HHAT was proposed as the likely candidate gene. The phenotypic overlap with the family we report herein provides further evidence implicating HHAT in cerebellar development and the pathogenesis of this rare spectrum.

Keywords

HHAT; Nivelon-Nivelon-Mabille syndrome; cerebellar vermis hypoplasia; microcephaly; missense variant.

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