Table 1

Summary of the different mutations found in the MECP2 gene in male patients

Mutation	Pos	RS	De novo	Affected XY relatives	Affected XX relatives	Mother XCI	Comments	Ref
MBD, methyl binding domain; MR, relative presenting mental retardation; NA, not available; Pos, position with respect to known functional domains in the MECP2 protein; PPM-X, psychosis, pyramidal signs and macro-orchidism; RS, number of times this mutation was identified in a girl with Rett syndrome (according to the IRSA MECP2 variation database, http://mecp2.chw.edu.au/), RTT, relative affected by RS; SNE, severe neonatal encephalopathy; TRD, transcription repression domain; XCI, X-chromosome inactivation.
Non-pathogenic variants are not listed.
Missense mutations
R133C	MBD	92	No	None	RTT/MR	85:15	Mother has mild MR	Masuyama et al¹⁰
S134C	MBD	12	No	None	Atypical RTT	98:2		Budden et al¹¹
E137G	MBD	0	No	MR	None	Random	Unclassified variant	Couvert et al¹²
A140V	MBD	0	No	Severe MR	Mild MR	Random	Unclassified variant	Orrico et al¹³
	MBD	0	No	Severe MR	None	Random	Unclassified variant	Couvert et al¹²
	MBD	0	No	PPM-X	Mild MR	Random	Unclassified variant	Klauck et al¹⁴
F157I	MBD	0	Yes				Unclassified variant	Kankirawatana et al¹⁵
T158M	MBD	191	No	SNE	RTT	99:1		Villard et al¹⁶
	MBD	191	Yes					Lynch et al¹⁷
R167W		0	No	Moderate MR	None	Random	Unclassified variant	Couvert et al¹²
P225L	TRD	0	Yes				Unclassified variant	Moog et al¹⁸
P322S		0	No	None	MR	Random	Mother has mild MR	Ventura et al¹⁹
							Unclassified variant
R344W		0	NA	NA	NA	NA	Unclassified variant	Laccone et al²⁰
P405L		0	No	None	MR	NA	Mother has mild MR	Moog et al²¹
							Unclassified variant
K417M		0	No	None	None	Random	Unclassified variant	Kankirawatana et al¹⁵
R453Q		0	NA	NA	NA	NA	Unclassified variant	Couvert et al¹²
In-Frame deletions
P387del80		0	No	Mild MR	None	100:0		Yntema et al²²
Frameshifts and nonsense mutations
G163fs		1	No		RTT	NA		Geerdink et al²³
G252fs	TRD	3	No	None	RTT		Germline mosaicism	Zeev et al²⁴
G269fs	TRD	9	No	None	RTT	Skewed	Mother has mild MR	Wan et al⁷
	TRD	9	Yes					Leuzzi et al²⁵
	TRD	9	Yes					Kankirawatana et al¹⁵
R270fs	TRD	3	Yes					Kankirawatana et al¹⁵
G273fs	TRD	0	Yes					Ravn et al²⁶
L386fs		7	No	None	None	95:5		Dayer et al²⁷
Q406X		0	No	Severe MR	None	Random	Mild MR in a carrier female	Meloni et al²⁸
E472fs		0	Yes					Kleefstra et al²⁹
Large duplications
430 kb		0	No	None	None	90:10	Duplication of AVPR2 to FLNA	Meins et al³⁰
0.4–0.8 Mb		0	No	Severe MR	None	>85:15	4 duplications	Van Esch et al³¹
0.4–0.8 Mb		0	No	Severe MR	None	>90:10	6 duplications	Friez et al³²
0.2–2.2 Mb		0	U	None	None	Skewed	6 duplications and 1triplication	Del Gaudio et al³³
Abnormal karyotypes
Y141X/XXY	MBD	6	Yes					Schwartzman et al³⁴
T158M/XXY	MBD	191	Yes				76% of XXY cells	Leonard et al³⁵
E455X/XX		1	Yes				Heterozygous male	Maiwald et al³⁶
Somatic mosaicism
P56fs		0	Yes					Clayton-Smith et al³⁷
R133H	MBD	3	Yes					Armstrong et al³⁸
T158M	MBD	191	Yes				25% mutant cells	Kleefstra et al³⁹
R270X	TRD	146	Yes				40% mutant cells	Topcu et al⁴⁰