Table 6.

Phenotype–genotype analysis (n = 35).

Locus	Mutation Type	Number	Clinical Outcome	Remarkable Phenotypes	References
Intron 5	Splice	3	Severe	Facial dysmorphisms, small head/microcephaly, axial hypotonia, peripheral spasticity, optical alterations, absent speech, severe ID, no eye contact, behavioral difficulties	Verhoeven et al. 2020 [1], Wang et al. 2019 [29]
Exon 6	Nonsense, frameshift	2	Severe	Facial dysmorphisms, small head/microcephaly, axial hypotonia, peripheral spasticity, severe speech impairment (no speech/2 words), severe ID, behavioral difficulties	Kuechler et al. 2015 [2], Kharbanda et al. 2017 [30]
Exon 4	Frameshift	1	Moderate-Severe	Facial dysmorphisms, microcephaly, axial hypotonia, peripheral spasticity, no walking, no speech (few words), autistic behavior	Kuechler et al. 2015 [2]
Exon 8	Missense	1	Moderate-Severe	Facial dysmorphisms, epilepsy microcephaly, axial hypotonia, peripheral spasticity, delayed walking, impaired speech (words not intelligible), ID	Kuechler et al. 2015 [2]
Exon 9	Nonsense	3	Moderate-Severe	Facial dysmorphisms, small head/microcephaly, optical alterations, axial hypotonia, peripheral spasticity, severe speech impairments (no speech/single words), severe ID and can have behavioral alterations	Kuechler et al. 2015 [2], Ligt et al. 2012 [4], Tucci et al. 2014 [28], Kharbanda et al. 2017 [30]
Exon 9	Frameshift	3	Moderate-Severe	Facial dysmorphisms, small head/microcephaly, optical alterations, axial hypotonia, peripheral spasticity, moderate speech (can have understandable words, can repeat short sentences), absent walking and speech, and can have behavioral difficulties	Kuechler et al. 2015 [2], Ligt et al. 2012 [4], Tucci et al. 2014 [28], Jin et al. 2020 [5], Kharbanda et al. 2017 [30]
Exon 10	Nonsense	2	Moderate-Severe	Facial dysmorphisms, small head/microcephaly, impaired speech (noises, few words), moderate/severe ID, behavioral difficulties	Kharbanda et al. 2017 [30]
Exon 11	Nonsense	1	Moderate-Severe	Facial dysmorphisms, optical alterations, axial hypotonia, unable to walk, impaired speech (few words), severe ID, behavioral difficulties	Kharbanda et al. 2017 [30]
Exon 12	Frameshift	2	Moderate-Severe	Facial dysmorphisms, optical alterations, peripheral spasticity, impaired speech (few words), ID	Kuechler et al. 2015 [2]
Exon 3	Nonsense, frameshift	2	Moderate	Facial dysmorphisms, optical alterations, axial hypotonia, peripheral spasticity, impaired speech (short sentences, unclear speech), ID	Winczewska-Wiktor et al. 2016 [23], Kuechler et al. 2015 [2]
Exon 4	Nonsense	1	Moderate	Facial dysmorphisms, microcephaly, axial hypotonia, peripheral spasticity, delayed walking, impaired speech (at 4 and 5 years < 50 words), ID, autistic behavior	Kuechler et al. 2015 [2]
Exon 5	Frameshift	1	Moderate	Facial dysmorphisms, strabismus, microcephaly, axial hypotonia, peripheral spasticity, delayed walking, impaired speech (simple sentences, read simple words), mild ID, and autistic behavior	Tucci et al. 2014 [28]
Exon 7	Nonsense, frameshift	4	Moderate	Facial dysmorphisms, axial hypotonia, peripheral spasticity, delayed walking (average 4,2 years), impaired speech (started speaking in 4 years, speaks in sentences, articulation poor), and can have behavioral difficulties	Ligt et al. 2012 [4], Tucci et al. 2014 [28], Kharbanda et al. 2017 [30]
Intron 7	Splice	1	Moderate	Facial dysmorphisms, microcephaly, axial hypotonia, peripheral spasticity, absent walking, impaired speech, ID	Kuechler et al. 2015 [2]
Exon 10	Nonsense	1	Moderate	Facial dysmorphisms, microcephaly, axial hypotonia, peripheral spasticity, impaired speech, autism	Kharbanda et al. 2017 [30]
Entire gene	Gross deletion	2	Moderate	Facial dysmorphisms, optical alterations, microcephaly, axial hypotonia, impaired walking, impaired speech, ID	Dubruc et al. 2014 [41], Kuechler et al. 2015 [2]
Exon 13	Nonsense	3	Mild	Facial dysmorphisms, axial hypotonia, delayed walking (before 24 months), mild ID, behavioral alteration (autism and aggression)	Kuechler et al. 2015 [2], Kharbanda et al. 2017 [30]
Exon 14 and 15	Missense and Nonsense	2	Normal	Normal phenotype with only optical alterations (FEVR)	Panagiotou et al. 2017 [35]