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Khajuria et al. J Transl Genet Genom 2020;4:91-103 I http://dx.doi.org/10.20517/jtgg.2020.06 Page 95

Table 1. List of MECP2 sequence variants identified in RTT patients in the present study
Exon/Intron Nt. change A.A change Origin Domain Recr.
a
a
intron 2 c.377+22C>G # - de-novo - 1
2.1 c.50dupA p.D17Fs de-novo NTR 1
2.2 c.210C>T # p.S70S de-novo NTR 1
2.2 c.274G>T p.G92X de-novo MBD 1
2.2 c.316C>T p.R106W de-novo MBD 2
2.2 c.375C>A # p.I125I de-novo MBD 1
intron 3 c.378-74C>T # - de-novo - 2
3.1 c.397C>T p.R133C de-novo MBD 5
3.1 c.401C>G p.S134C de-novo MBD 1
3.1 c.413T>C p.L138S de-novo MBD 1
3.1 c.455C>G p.P152R de-novo MBD 3
3.1 c.468C>G p.D156E de-novo MBD 1
3.1 c.471 C>G p.F157L de-novo MBD 1
3.1 c.473C>T p.T158M de-novo MBD 8
3.1 c.484dupA p.R162fs de-novo MBD 1
3.1 c.502C>T p.R168X de-novo ID 7
3.2 c.683C>G # p.T228S de-novo TRD 1
3.2 c.763C>T p.R255X de-novo TRD/NLS 5
3.2 c.784C>T p.Q262X de-novo TRD 1
3.2 c.806delG p.G269fs de-novo TRD 5
3.3 c.808C>T p.R270X de-novo TRD/NLS 8
3.3 c.808delC p.R270fs de-novo TRD/NLS 1
3.3 c.834C>T # p.A278A de-novo TRD/NLS 1
3.3 c.856_859delAAAG p.K286fs de-novo TRD 1
3.3 c.869dupA p. E290fs de-novo TRD 1
3.3 c.880 C>T p.R294X de-novo TRD 1
3.3 c.916C>T p.R306C de-novo TRD 5
4.1 c.1151_1188del38 p.P384fs de-novo CTR 1
4.1 c.1157_1200del44 p.L386Fs de-novo CTR 2
4.1 c.1180G>A # p.E394K de-novo CTR 1
4.2 c.1284C>T # p.G428G de-novo CTR 1
4.2 c.1452dupAG p.V485fs de-novo CTR 1
4.2 c.1455dupTA p. S486fs de-novo CTR 1
ex 3.1 upto ex 4.1 c.378-?_c.1017+?del « - de-novo MBD, TRD, CTR 2
int 2 upto 3’UTR c.27-?_c.1396+?del « - de-novo MBD, TRD, CTR 2
ex 4.1 upto 3’UTR c.1396-?_c.X5349+?del « - N.T MBD, TRD, CTR 1
int 2 upto ex 4.1 c.27-?_c.1017+?del « - N.T MBD, TRD, CTR 1
3’UTR c.X5349-?_c.5349+?del « - N.T 3’UTR 1
«
a Numbered according to the GenBank accession number NM_04992.3; the exact nomenclature was very difficult as we did not
#
sequence the deletion variants and therefore do not know the exact breakpoints; these variants were found along with another variant
in the same patient. Nt.: nucleotide; A.A: amino acid; Recr.: recurrence; N.T: not tested due to unavailability of parents; NTR: N-terminal
region; ex: exon; int: intron; MBD: methyl binding domain; TRD: transcription repression domain; ID: interdomain; CTR: C terminal region;
UTR: un-translated region; RTT: Rett syndrome

Thirteen novel MECP2 variants were identified in this study in the RTT patients [Table 3], which included
four large deletions, six frameshift [p.D17fs (GenBank accession No. FJ212168.1), p.R162fs (GenBank
accession No. GU812285.1), p.E290fs (GenBank accession No. GQ203293.1), p.P384fs (GenBank accession
No. FJ212171.1), p.V485fs (GenBank accession No. HQ141378), and p.S486fs (GenBank accession No.
GQ203295.1)], one missense p.L138S, one synonymous p.G428G (GenBank accession No. FJ212169.1), and
one nonsense (p.G92X) variant [Table 3 and Figure 1].

Seven RTT patients were found carrying more than one variant in MECP2 gene [Table 1]. One of the RTT
patients carrying p.L386fs mutation was also carrying a novel synonymous change p.G428G (c.1284C>T).
In two patients carrying mutation p.R270X, one of them was also carrying synonymous change p.S70S