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. 2019 Oct;6(10):2097-2103.
doi: 10.1002/acn3.50898. Epub 2019 Sep 26.

Targeted SLC19A3 gene sequencing of 3000 Saudi newborn: a pilot study toward newborn screening

Majid Alfadhel  1   2   3 , Muhammad Umair  2   3 , Bader Almuzzaini  2 , Saif Alsaif  3   4 , Sulaiman A AlMohaimeed  5 , Maher A Almashary  5 , Wardah Alharbi  2 , Latifah Alayyar  2 , Abdulrahman Alasiri  2 , Mariam Ballow  2 , Abdulkareem AlAbdulrahman  2 , Monira Alaujan  2 , Marwan Nashabat  1 , Ali Al-Odaib  6   7 , Waleed Altwaijri  3   8 , Ahmed Al-Rumayyan  3 , Muhammad T Alrifai  3 , Ahmed Alfares  9   10 , Mohammed AlBalwi  2   3   9 , Brahim Tabarki  11
Affiliations

Targeted SLC19A3 gene sequencing of 3000 Saudi newborn: a pilot study toward newborn screening

Majid Alfadhel et al. Ann Clin Transl Neurol. 2019 Oct.

Abstract

Background: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is an autosomal recessive neurometabolic disorder mostly presented in children. The disorder is described as having subacute encephalopathy with confusion, dystonia, and dysarthria triggered by febrile illness that leads to neuroregression and death if untreated. Using biotin and thiamine at an early stage of the disease can lead to significant improvement.

Methods: BTBGD is a treatable disease if diagnosed at an early age and has been frequently reported in Saudi population. Keeping this in mind, the current study screened 3000 Saudi newborns for the SLC19A3 gene mutations using target sequencing, aiming to determine the carrier frequency in Saudi Population and whether BTBGD is a good candidate to be included in the newborn-screened disorders.

Results: Using targeted gene sequencing, DNA from 3000 newborns Saudi was screened for the SLC19A3 gene mutations using standard methods. Screening of the SLC19A3 gene revealed a previously reported heterozygous missense mutation (c.1264A>G (p.Thr422Ala) in six unrelated newborns. No probands having homozygous pathogenic mutations were found in the studied cohort. The variant has been frequently reported previously in homozygous state in Saudi population, making it a hot spot mutation. The current study showed that the carrier frequency of SLC19A3 gene mutation is 1 of 500 in Saudi newborns.

Conclusion: For the first time in the literature, we determined the carrier frequency of SLC19A3 gene mutation in Saudi population. The estimated prevalence is too rare in Saudi population (at least one in million); therefore, the data are not in favor of including such very rare disorders in newborn screening program at population level. However, a larger cohort is needed for a more accurate estimate.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A, B) Schematic representation of SLC19A3 exons and protein domains representing the identified mutations reported to‐date
See this image and copyright information in PMC

References

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