Table 2.
Disease causing variants detected in Egyptian children with maple syrup urine disease (MSUD) (n = 10).
| Family | Patient | Chromosomal location (GRCh38) |
Gene: Nucleotide change* | Exon/Intron | Protein effect*/ Zygosity | Zygosity | Variant effect | rsID | ACMG classification | ClinVar | MAF exomes/ genomes | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I | 1 | Chr6-80343774-T-A | BCKDHB:c.1149T > A | Exon 10 | p.(Tyr383Ter) | H | Nonsense | rs190867671 | Pathogenic | P/LP |
0.00/ 0.00 |
Henneke et al., 2003 |
| II | 2,3 | Chr6-80273153-C-T | BCKDHB:c.970 C > T | Exon 9 | p.(Arg324Ter) | H | Nonsense | rs398124603 | Pathogenic | P/LP |
0.0000598/ 0.0000132 |
McConnell et al., 1997; Puckett et al.,2010 |
| III | 4 | Chr19-41419282-C-T | BCKDHA:c.632 C > T | Exon 5 | p.(Thr211Met) | H | Missense | rs398123503 | Pathogenic | P/LP |
0.000024/ 0.00000657 |
Georgiou et al.,2009 |
| IV | 5 | Chr19-41424582-T-A | BCKDHA:c.1312T > A | Exon 9 | p.(Tyr438Asn) | H | Missense | rs137852870 | Pathogenic | P/LP |
0.0000643/ 0.000118 |
Zhang et al.,1989; Henneke et al., 2003 |
| V | 6 | Chr19-41422163-G-C | BCKDHA:c.647-1G > C | Intron 5–6 | ----- | H | Splicing | rs753216964 | Pathogenic | P |
0.00/ 0.00000657 |
Jaradat et al.,2015 |
| VI | 7 | Chr6-80127496-80171441dup | BCKDHB | Exons 2–6 duplication | ----- | H | CNV | ----- | VUS | ----- |
0.00/ 0.00 |
This study |
| Chr6-87521473-C-T | RARS2:c.1026G > A | Exon 12 | p.(Met342lle) | H | Missense | rs34647222 | Likely Pathogenic | P/LP/ VUS |
0.000255/ 0.000158 |
Pronicka et al.,2016 | ||
| VII | 8 | Chr1-100196413-G-A | DBT:c.1291 C > T | Exon 11 | p.(Arg431Ter) | H | Nonsense | rs398123660 | Pathogenic | P/LP |
0.00000843/ 0.0000187 |
Sun et al.,2020 |
| VIII | 9 | Chr6-80343716-A-G | BCKDHB:c.1091 A > G | Exon 10 | p.(Asp364Gly) | H | Missense | ----- | Likely Pathogenic | ----- |
0.00/ 0.00 |
Khalifa et al., 2020 |
| IX | 10 | Chr6-80203114-C-T | BCKDHB:c.853 C > T | Exon 8 | p.(Arg285Ter) | H | Nonsense | rs398124598 | Pathogenic | P/LP |
0.0000137/ 0.000145 |
Henneke et al., 2003 |
*Variants nomenclature is according to BCKDHA: NM_000709.4 and NP_000700.1; BCKDHB: NM_183050.4 and NP_898871.1; DBT: NM_001918.5 and NP_001909.4; RARS2: NM_020320.4 and NP_064716.2 Refseq gene transcript and protein, respectively; MAF, minor allele frequency according to gnomAD population database (https://gnomad.broadinstitute.org/); H, homozygous. All variants segregated properly in both parents of the diseased children according to strict autosomal recessive inheritance.