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Table 1 Clinical features of described patients with MED13L missense mutations and in silico-analysis results of these mutations

From: Report of a de novo c.2605C > T (p.Pro869Ser) change in the MED13L gene and review of the literature for MED13L-related intellectual disability

Literature Our case [2] [15] [16] [17] [18] [14] [19] [13]
Mutations c.2605C > T (Pro869Ser) c.752A > G (Glu251Gly) c.5615G > A (Arg1872His) c.6068A > G (Asp2023Gly) c.4247G > A (Arg1416His) c.2579A > G (Asp860Gly) c. 5371 A > T (Ser1791Cys) c.5695G > A (Gly1899Arg) c.2579A > G (Asp860Gly) c.5282C > T (Prol1761Leu) c.187 T > C (Cys63Arg)
Inheritance De novo maternally inherited inheritance: NM inheritance: NM homozygous De novo Paternally inherited De novo De novo NM De novo
Exon 15 6 25 28 19 15 24 25 15 23 2
Domain   N-terminal domain C-terminal domain C-terminal domain MID-MedPIWI α-helical sequence   C-terminal domain α-helical sequence C-terminal domain N-terminal domain
SIFT damaging damaging tolerated tolerated damaging tolerated damaging damaging tolerated tolerated damaging
Polyphen2 probably damaging possibly damaging probably damaging probably damaging probably damaging probably damaging probably damaging probably damaging probably damaging benign probably damaging
Mutation taster disease causing disease causing disease causing disease causing disease causing disease causing disease causing disease causing disease causing polymorphism disease causing
mRNA expression levels are significantly decreased revealed by qRT-PCR
ID + Except dTGA, there are no other clinical features provided in these three patients + + + + + + +
Speech impairment + NM NM + + + + +
Delayed milestones + NM NM NM + + + +
Growth parameter weight low NM NM NM low NM NM NM
height short     NM NM NM NM NM NM
Head deformities microcephaly     NM NM NM NM NM NM NM
Behavioral difficulty/autism +     NM NM + Autism/auto-aggression poor attention
span
anxiety and disruptive and aggressive behavior Self-harm, autism
Hypo- or hyper-tonia Hypotonia     NM NM NM Hypotonia Hypotonia Hypotonia/feeding difficulties Hypotonia since birth whereas turn hypertonic since 4 y 10 m
Craniofacial deformity and other dysmorphic features frontal
bossing, low-set ears, hypertelorism, epicanthus,
depressed nasal bridge, bulbous nasal tip, cupid-bow upper lip combined with open mouth appearance, micrognathia
    NM small dysplastic low-set ears,
bulbous nasal tip,
large mouth,
single transverse palmar crease of the right hand
No dysmorphic features asymmetric face, strabismus, left eye ptosis, ocular hypertelorism, downslanting palpebral
fissures, bilateral epicanthus, wide, depressed nasal root, tented
upper lip with frequent drooling, and low set ears
squared, low set ears with rather narrow ear lobes,
mild ptosis,
flat malar region, mild broadening of the nose, retrognathia
right-sided torticollis, asymmetric facies with simple uncurled slightly low-set right ear that protrudes from
the head, enlargement or protrusion of the skull, and two small cafe au lait spots
reduced palpebral fissures, nasal base enlargement, enlarged plane philtrum, a
thin upper lip, low-set ears, and a prominent columella
Cardiac anomalies mild aortic coarctation,
mild aortic regurgitation,
slight tricuspid regurgitation
dTGA dTGA dTGA NI NM NM patent ductus arteriosus NI atrial septal defect NI
Urinary system Congenital UPJO combined with high ureter attachment of right     NM NM NM NM NI NM NM
Miscellaneous Odontoprisis, appendicular muscular atrophy, hyperlaxity of the joints, scoliosis, spontaneous facture of femur        unilateral hearing loss, atopic dermatitis With no muscle weakness, but was still clumsy, some hyperlaxity of the joints and skin   
Epileptic seizure No clinically observed seizures     NM + NM + intractable atonic or absence seizures NM
MRI abnormalities enlarged bilateral lateral ventricles at 5 months old     NM NM NM a prominence of subarachnoid
space, predominantly frontal, ventriculomegaly and mega cisterna
magna
mild dilatation of the lateral ventricles,
a segmental thinning of the posterior part of the body of the corpus callosum
NM Normal at 3 y 5 m
EEG abnormalities spike and slow wave colligation and multi-spike and slow waves in bilateral occipital and posterior temporal region, as well as rapid rhythm distribution in the occipital area     NM NM NM Normal NM NM frequent epileptiform discharges during sleep in the left parietotemporal region and in the right centrotemporal region in absence of continuous spikes and waves during slow-wave sleep
Literature [12] [11] Proportion (for the 18 patients who phenotypes are reported)
P14 P20 P21 P22 P23 P28 P32 P33 P35
Mutations c.6485C > T (Thr2162Met) c.2597C > T (Pro866Leu) c.6488C > T (Ser2163Leu) c.2930C > T (Ala977Val) c.6488C > T (Ser2163Leu) c.2605C > T (Pro869Ser) c.6530C > A (Ser2177Tyr) c.6005C > T (Ser2002Leu) c.2605C > T (Pro869Ser) c.3392G > A (Cys1131Tyr)  
Inheritance De novo De novo NM De novo De novo De novo De novo De novo De novo De novo  
Exon 30 15 30 16 30 15 31 27 15 17  
Domain C-terminal domain   C-terminal domain   C-terminal domain   C-terminal domain C-terminal domain    
SIFT damaging damaging damaging tolerated damaging damaging damaging   damaging   
Polyphen2 probably damaging probably damaging probably damaging probably damaging probably damaging probably damaging probably damaging probably damaging probably damaging probably damaging  
Mutation taster disease causing disease causing disease causing disease causing disease causing disease causing disease causing disease causing disease causing disease causing  
ID + +(severe) + (severe) + + (severe) + + + + + 18/18 (100%)
Speech impairment + + + + + + + + + + 16/18 (88.9%)
Delayed milestones + + + + + + + + + + 15/18 (83.3%)
Growth parameter weight NM NM NM NM NM NM NM NM NM low 3/18 (16.7%)
height NM NM NM NM NM NM NM NM NM short 2/18 (11.1%)
Head deformities NM NM NM NM NM NM NM NM NM NM 1/18 (5.6%)
Behavioral difficulty/autism Autistic features Autistic features Autistic features and behavioral
troubles
NM Autistic features and behavioral
troubles
10/18 (55.6%)
Hypo- or hyper-tonia Hypotonia Hypotonia Hypotonia Hypotonia Hypotonia Hypotonia /Feeding difficulties Severe
Hypotonia/Feeding difficulties
12/18 (66.7%)
Craniofacial deformity and other dysmorphic features hypotonic
open-mouth, Thin vermillon
border
Hypotonic
open-mouth, Bulbous nasal
tip
Hypotonic
open-mouth, Bulbous nasal
tip
Up-slanting
palpebral
fissures, Bulbous nasal
tip, Cupid-bow
upper lip, Hypotonic
open-mouth, Thin vermillon
border, Deep philtrum
Up-slanting
palpebral
fissures, Bulbous nasal
tip, Cupid-bow
upper lip, Hypotonic
open-mouth, Thin vermillon
border, Deep philtrum, clinodactyly
Bilateral club foot Up-slanting
palpebral
fissures, Bulbous nasal tip, Thin vermillon
border, ectopic anus, bilateral talipes, colo-bomatous micro-phtalmia
Up-slanting
palpebral
fissures, Bulbous nasal
tip, Cupid-bow upper lip, Hypotonic
open-mouth, Thin vermillon
border, Deep philtrum
Displaced right pupil, bilateral microphthalmia, irido-corneal synechiae on the left, frontal
bossing, short palpebral fissures, long eye lashes, broad straight eyebrows, depressed nasal bridge, Open mouth
appearance, protrusion of the tongue
15/18 (83.3%)
Cardiac anomalies NI NI NI NI NI coarctation of the aorta NI patent foramen ovale NI NI 5/18 (27.8%)
Urinary system Kidney cysts NM NM NM NM double ureter NM NM NM NM 3/18 (16.7%)
Miscellaneous   Nystagmus, craniosynostosis, ataxia    Vertebral artery occlusion, ataxia Intrauterine growth retardation Ataxia Intrauterine growth retardation Hearing
Impairment, myopia
Inguinal hernia in neonatal period, spastic paraparesis, dystonic movements of the extremities and the tongue,  
Epileptic seizure + + + + + 8/18 (44.4%)
MRI abnormalities Normal Normal Normal Focal cortical dysplasia NM Hypomyelination NM Ventriculo-Megaly Diffuse cortical atrophy a slightly enlarged ventricular system, partial agenesis of the corpus callosum, and a Dandy-Walker variant 8/12 (66.7%)
EEG abnormalities NM NM NM NM NM NM NM NM NM NM 2/18 (11.1%)
  1. NM Not mentioned, NI Not involved, dTGA dextro-looped transposition of the great arteries