First Report of PIGT Mutant Among the Libyan Population that Cause Multiple Congenital Anomalies, Hypotonia, Seizure Syndrome (MCAHS3) by A New Gene Mutation: A CASE REPORT

الملخص

Multiple congenital anomaly hypotonia seizure syndrome 3(MCAHS3) is a rare inherited neurological disease
due to mutation of the PIGT gene (OMIM615398). MCAHS3 is characterized by multiple congenital anomalies
(cardiac. Renal and skeletal), severe hypotonia from an early age, and usually is associated with refractory seizures.
This study described phenotypic and genotypic findings of a case and compared them to previously described cases.
This study also highlighted the importance of Whole-Exome Sequencing in the diagnosis of rare neurological
diseases. A severe hypotonic ten-month-old Libyan girl, a product of consanguineous marriage was admitted at the
age of one month.Her results of Whole-Exome Sequencing revealed homozygous missense variant c.1519C>T(p.
Arg507Trp). The PIGT gene revealed multiple congenital anomaly hypotonia seizure 3 diseases due to the PIGT
gene. Comparing our case with the ten previously reported cases, all shared clinical presentation of hypotonia,
some dysmorphic features, EEG findings. The congenital anomalies and low alkaline phosphatase are a feature of
some cases. Lastly, the seizure is reported in all cases. In our case, she had two attacks of convulsion with fever.
Whole-Exome Sequencing is a vital tool for diagnosing this rare neurological disease.c.1519 C>T(p.Arg507Trp)
in PIGT has been described 6 times heterozygously in the gnom AD for the control population, but it has not been
described in homozygous situation. We considered homozygous c.1519 C>T (p.Arg507Trp) in PIGT as a likely
pathogenic variant and causal to the clinical phenotypes observed in our patient. However, the coexistence of
developmental delay, hypotonia, and epilepsy together with multiple congenital anomalies, especially anorectal
anomalies, should lead a clinician to consider a GPI deficiency-related disorder.