Novel compound heterozygous GPR56 gene mutation in a twin with lissencephaly: A case report

Table 1 Summary of GPR56 mutations

Ref.	Mutation	Exon/intron	Case number	Ethnicity	Consanguinity	Motor delay	Cognitive delay	Seizure	MRI
									Gyri	White matter abnormalities	Brainstem/cerebellum
Piao et al[10,11], 2004 and 2005	c.112C>T (p.R38W)	Exon 3	2	Arabic (Qatar)	First cousin	+	Moderate	GTC, myoclonic	BFPP	Patchy signal change	Small brainstem
						+	NA	+
			1	Arabic (UAE)	First cousin	+	+	NA	BFPP	Reduced volume, patchy signal change	Slightly small pons and vermis
	c.113G>A (p.R38Q)	Exon 3	1	Turkish	First cousin	+	+	+	BFPP	Severely reduced volume, patchy signal change	Small pons and vermis
	c.263A>G (p.Y88C)	Exon 3	2	French Canadian	N	+	+	NA	BFPP	Reduced volume, patchy signal change	Small pons, small/dysplastic cerebellum
	c.739-746 delCAGGACC (p.Q246Tfx*72)	Exon 5	2	Indian	N	+	+	Blank episodes	BFPP	Reduced volume, patchy signal change	Slightly small pons and vermis
						+	+	AS
			1	Pakistani	First cousin	Severe	Severe	Generalized	BFPP	Patchy radiolucency	Small cerebellum
			1	Afghani	First cousin	Moderate	+	NA	BFPP	Reduced volume, patchy signal change	Small pons and superior vermis
	c.E5- 1G>C (NA)	Exon 5	2	Palestinian	N	+	+	Episodes of startles	BFPP	Reduced volume, periventricular signal change	Small pons and superior vermis
	c.1036T>A(p.C346S)	Exon 8	2	Palestinian	First cousin	+	+	NA	BFPP	Reduced volume, patchy signal change	Small pons and cerebellum
			1	Palestinian	First cousin	+	Severe	+	BFPP	Reduced volume, frontal subcortical signal change	Small brainstem and cerebellum
	c.1046G>C(p.W349S)	Exon 8	2	Israeli Jewish	First cousin	+	+	GTC	BFPP	Reduced volume, patchy signal change	Small pons and vermis
						+	+	Myoclonic	BFPP
			1	Israeli Jewish	N	+	Severe	+	BFPP	Patchy signal change	Small vermis
	c.IVS9+3G>C (NA)	Intron 9	3	Palestinian	First cousin	+	+	FS, atonic-drop	BFPP	Patchy signal change	Slightly small pons and superior vermis
						+	Moderate	GTC, AS	BFPP
						Severe	Severe	FS, GTC	BFPP
			2	Palestinian	First cousin	+	Severe	GTC, atonic	BFPP	Patchy signal change	Small pons and superior vermis
						+	Severe	No	BFPP
	c.1693C>T (p.R565W)	Exon 13	3	Arabic (Bedouin)	C	+	Severe	GTC, myoclonic	BFPP	Reduced volume, patchy signal change	Small vermis
			1	Italian	Second cousin	+	+	+	BFPP	Reduced volume, patchy signal change	Slightly small vermis
	c.1919T>G (p.L640R)	Exon 13	1	Hispanic	N	+	+	+	BFPP	Mildly reduced volume, patchy signal change	Slightly small cerebellar hemispheres
Parrini et al[18], 2009	c.97C>G (p.R33P)	Exon 2	2	Turkish	C	+	Severe	Atypical absences, GTC, tonic	BFPP	NA	NA
						+	Severe	Tonic, atypical absences, recurrent nonconvulsive status epilepticus	BFPP	Patchy signal change	NA
	c.235C>T (R79X)	Exon 2	1	Italian	C	+	Severe	Infantile spasms, tonic and atonic seizures	BFPP	Patchy signal change	NA
	c.1693C>T (p.R565W)	Exon 13	1	Italian	C	+	Severe	Tonic atonic GTC, atypical absences, recurrent nonconvulsive statusepilepticus	BFPP	Patchy signal change	Slightly small vermis
Bahi-Buisson et al[19], 2010	c.174-175insC (p.E59Rfs*24)	Exon 3	2	NA	C	NA	Severe	+	NA	NA	NA
						Walking at 4 yr	Severe	Focal seizures	BFPP	Patchy periventricular predominance	Hypoplastic pons
	c.272G>A (p.C91Y)	Exon 3	2	NA	C	Walking at 2 yr	Severe	NA	BFPP	Patchy	Hypoplastic pons
						Walking at 2 yr	Severe	GTC/atypical absence, atonic seizures	BFPP	Patchy periventricular and frontal predominance	Hypoplastic pons, Cyst in the ventral pons
	c.367C>T (p.Q123X)	Exon 3	1	NA	C	+	Severe	Focal seizures, GTC	BFPP	Patchy periventricular and frontal predominance	Hypoplastic pons, Cyst in the ventral pons
	c.671delA (p.D224Wfs*96)	Exon 5	3	NA	C	Walking at 4 yr	Severe	GTC	BFPP	Patchy periventricular and frontal predominance	Hypoplastic pons
						Walking at 18 mo	Severe	GTC	BFPP
						Sitting without support	Severe	GTC	BFPP	Diffuse	Hypoplastic pons
	c.1215-1216delC (p.L406S406fs*41)	Exon 10	1	NA	C	Walking acquired but subsequently lost (11 yr)	Severe	+	BFPP	Patchy	Hypoplastic pons
	c.1254C>G (p.C418W)	Exon 10	3	Pakistani	First cousin	Walking at 5 yr	Severe	GTC	BFPP	Diffuse	Hypoplastic pons
						Walking at 5 yr	Severe	GTC	BFPP	Patchy with subcortical and frontal predominance, reduced volume	Severely hypoplastic pons with posterior concavity, cyst in the ventral pons
						NA	NA	NA	NA	NA	NA
	c.1345delCTG (p.L449del)	Exon 11	1	NA	C	Walking at 3 yr	Severe	Atypical absence	BFPP	Patchy with subcortical predominance	Severely hypoplastic pons with posterior concavity
	c.1453C>T (p.S485P)	Exon 11	2	NA	C	Walking at 18 mo	Severe	Focal seizures, generalized tonic seizures	BFPP	Patchy with subcortical and frontal predominance	Hypoplastic pons
						Walking at 18 mo	Severe	Focal seizures	BFPP
Luo et al[20], 2011	c.1486G>A (p.E496K)	NA	1	Yemeni	First cousin	Walking	Severe	Tonic-clonic seizures	BFPP	Asymmetric areas of abnormal signal in the white matter of both cerebral hemispheres	Mild hypoplasia of the inferior cerebellar vermis and pons
Quattrocchi et al[16], 2013	c.105C>A (p.C35X)	Exon 2	1	NA	NA	Ataxic gait	Severe	Focal seizures, myoclonic	BFPP	Patchy subcortical and periventricular white matter abnormalities	Mildly hypoplastic cerebellar vermis, flattening of the ventral aspect of the pons, hemispheric cerebellar cysts, vermian cysts
	c.429G>A (p.W143X)	Exon 2	1	NA	NA	Ataxic gait	Moderate	No	BFPP	Patchy subcortical and periventricular white matter abnormalities	Mildly hypoplastic cerebellar vermis, flattening of the ventral aspect of the pons, hemispheric cerebellar cysts, vermian cysts
	c.1453C>T (p.S485P)	Exon 11	2	NA	NA	Walking at 18 mo	Severe	GTS, focal seizures	BFPP	Patchy subcortical and periventricular white matter abnormalities	Hypoplastic pons and superior vermis, hemispheric cerebellar cysts, vermian cysts
						Walking at 22 mo	Severe	Focal seizures	BFPP	Patchy subcortical and periventricular white matter abnormalities	Hypoplastic pons and superior vermis, hemispheric cerebellar cysts, vermian cysts
	c.1796-1801delTGCGCC/insAGATCCTGTGGGCAGAT (premature stop codon at position 614)	Exon 12	1	NA	NA	Ataxic gait	Moderate	No	BFPP	Patchy subcortical and periventricular white matter abnormalities	Flattening of the ventral aspect of the pons, hemispheric cerebellar cysts
Fujii et al[21], 2014	c.107G>A and c.113G>A(p.S36N and p.R38Q)	Exon 2	1	Japanese	N	Able to walk with help	Severe	Complex partial seizures, tonic seizures, epileptic spasms	BFPP	Patchy high signals in the frontal subcortical	Hypoplastic pons
Desai et al[22], 2015	c.113G>A (p.R38Q)	Exon 3	1	Indian (Marathi)	C	Mode-rate	Moderate	Complex febrile seizures	BFPP	Diffuse	Mild thinning and cerebellar cysts
	c.739–746 delCAGGACC (p.Q246Tfx*72)	Exon 4	1	Indian (Punjabi)	N	Severe	Mild	No	BFPP	Frontal and periventricular	Mild thinning and cerebellar cysts
	c.739–746 delCAGGACC (p.Q246Tfx*72)	Exon 4	1	Indian (Sindhi)	N	Severe	Moderate	No	BFPP	Frontal and periventricular	Inferior vermian hypoplasia; cerebellar cyst
	c.1426 C>T (p.R476X)	Exon 12	1	Indian (Gujarati)	C	Severe	Severe	Generalized seizures	BFPP	Diffuse	Mild thinning and cerebellar cysts
Santos-Silva et al[17], 2015	811C > T (R271X)	Exon 6	1	Caucasian	N	Severe	Severe	Hot water epilepsy	BFPP	Reduced volume, patchy signal change	Hypoplasia of the pons and cerebellar vermis
Öncü-Öner et al[14], 2018	811C > T (R271X)	Exon 6	1	NA	C	Severe	Severe	Focal onset bilateral tonic-clonic seizure	BFPP	Yes	Thin brainstem and normal cerebellar structure
Current report	c.228delC and c.1820-1821del AT (p.F76fs and p.H607fs)	Exon 6 and Exon 13	2	Chinese	N	+	Severe	GTC	LIS	Reduced volume, patchy signal change	Normal
						+	+	No	LIS	NA	NA

AS: Absence of seizure; BFPP: Bilateral frontoparietal polymicrogyria; C: Consanguineous; FS: Febrile seizure; GTC: General tonic-clonic seizures; LIS: Lissencephaly; MRI: Magnetic resonance imaging; N: Nonconsanguineous; NA: Not available; UAE: United Arab Emirates.