Table 1 Summary of clinical and molecular findings.
From: Overview of genetic variants in a cohort of Iranian patients with leukodystrophy
Case number | Gene | Transcript | Variant | Associated disease | OMIM | Inheritance | Zygosity | ACMG classification | Clinvar | dbSNP rsID | Age | Sex | Consanguinity | Clinical signs |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | RARS1 | NM_002887 | c.2T > C | Leukodystrophy, hypomyelination, 9 | 616,140 | AR | Hom | Pathogenic | Pathogenic | rs769713780 | 2 years | Male | Yes | Motor delay, vision loss, speech delay |
2 | RARS1 | NM_002887.4 | c.2T > C | Leukodystrophy, hypomyelinating, 9 | 616,140 | AR | Hom | Pathogenic | Pathogenic | rs769713780 | 1 year | Female | Yes | Microcephaly, global developmental delay |
3 | RARS1 | NM_002887.4 | c.2T > C | Leukodystrophy, hypomyelinating, 9 | 616,140 | AR | Hom | Pathogenic | Pathogenic | rs769713780 | 2 years | Male | Yes | Seizure, spasticity, developmental regression and motor delay |
4 | RARS1 | NM_002887.4 | c.2T > C | Leukodystrophy, hypomyelinating, 9 | 616,140 | AR | Hom | Pathogenic | Pathogenic | rs769713780 | 6 months | Female | Yes | Seizure, restlessness, recurrent vomiting, hypotonia, microcephaly |
5 | RARS1 | NM_002887.4 | c.2T > C | Leukodystrophy, hypomyelinating, 9 | 616,140 | AR | Hom | Pathogenic | Pathogenic | rs769713780 | 2.5 years | Female | Yes | Microcephaly, motor and developmental delay, speech delay and nystagmus |
6 | RARS1 | NM_002887 | c.2T > C | Leukodystrophy, hypomyelination, 9 | 616,140 | AR | Hom | Pathogenic | Pathogenic | rs769713780 | 4 months | Male | Yes | Microcephaly, motor delay and hearing impairment |
c.1716G > A | Het | Pathogenic | Likely pathogenic | - | ||||||||||
c.1912T > A | Het | VUS | VUS | rs13866496 | ||||||||||
7 | GJC2 | NM_020435 | c.733T > A | Spastic paraplegia 44, autosomal recessive Leukodystrophy, hypo myelinating | 613,206 608,804 | AR AR | Hom | Pathogenic | Likely pathogenic | rs62323857 | 7 months | Female | Yes | Nystagmus, motor delay, delayed myelination in brain MRI |
8 | PLEKHG2 | NM_022835 | c. 2920G > C | Leukodystrophy and acquired microcephaly with or without dystonia | 616,763 | AR | Hom | VUS | VUS | rs1193237988 | 17 years | Female | Yes | Seizure, developmental delay, speech delay, strabismus and ataxia. Her brother had the same disease |
9 | TMEM63A | NM_014698.3 | c.1493_1495delinsCCC | Leukodystrophy, hypomyelination, 19, transient infantile | 618,688 | AD | Het | VUS | – | – | 6 years | Female | No | Progressive muscle weakness, ataxia and Gowers’ sign |
10 | RNF220 | NM_018150 | c.1088G > A | Leukodystrophy, hypomyelination, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy | 619,688 | AR | Hom | VUS | Pathogenic | rs780921270 | 14 years | Female | Yes | Developmental delay, progressive ataxia, and progressive hearing loss. She had brain tumor since she was 7 |
11 | POLR1C | NM_203290 | c.364T > A | Leukodystrophy, hypomyelination, 11 Treacher Collins syndrome 3 | 616,494 248,390 | AR | Hom | Pathogenic | Likely pathogenic | rs1554131502 | 17 years | Male | Yes | Motor regression from age7 and hypomyelination of white mater in brain MRI |
12 | TUBB4A | NM_006087.4 | c.785G > A | Leukodystrophy, hypomyelinating, 6 | 612,438 | AD | Het | Pathogenic | Pathogenic/likely pathogenic | rs886039470 | 11 months | Female | Yes | Hypotonia, motor delay, normal metabolic test and normal EMG/NCV |
13 | DEGS1 | NM_003676.4 | c.764 A > G | Leukodystrophy, hypomyelinating, 18 | 618,404 | AR | Hom | Likely pathogenic | Pathogenic | rs768180196 | 2 years | Female | Yes | Motor and developmental delay, speech delay and hypo myelination in brain MRI |
14 | ACER3 | NM_018367 | c.607 C > T | Leukodystrophy, progressive, early childhood-onset | 617,762 | AR | Hom | Pathogenic | Pathogenic | rs782709009 | 22 months | Female | Yes | Motor regression, Elevated 3-Hydroxy butyric acid |
