Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly

Fallet-Bianco, Catherine; Laquerrière, Annie; Poirier, Karine; Razavi, Ferechte; Guimiot, Fabien; Dias, Patricia; Loeuillet, Laurence; Lascelles, Karine; Beldjord, Cherif; Carion, Nathalie; Toussaint, Aurélie; Revencu, Nicole; Addor, Marie-Claude; Lhermitte, Benoit; Gonzales, Marie; Martinovich, Jelena; Bessieres, Bettina; Marcy-Bonnière, Maryse; Jossic, Frédérique; Marcorelles, Pascale; Loget, Philippe; Chelly, Jamel; Bahi-Buisson, Nadia

doi:10.1186/2051-5960-2-69

Table 1 Neuropathology overview of foetuses interrupted for tubulin related microlissencephaly

From: Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly

Case number	*Gene*	Gender	Nucleotidic change	Proteic change	TOP	Cortical lamination	Neuronoglial overmigration	Heterotopia	Olfactory bulbs agenesis	Hippocampus	Enlarged GZ	Basal Ganglia	Corpus callosum	Cerebellum	Pons –Braintem	Ophthalmological signs	Head circumference	Additional morphological signs	Reference
Case number	*Gene*	Gender	Nucleotidic change	Proteic change	TOP	Cortical lamination	Neuronoglial overmigration	Heterotopia	Olfactory bulbs agenesis	Hippocampus	Enlarged GZ	Basal Ganglia	Corpus callosum	Cerebellum	Nuclei and corticospinal tract	Ophthalmological signs	Head circumference	Additional morphological signs	Reference
LIS_TUB_008_ fœtus13	TUBB2B	M	c.716G > T	p.C239F	16	Absent CP (2 layers including molecular layer)	Focal	-	N/A	N/A	+	N/A	c.ACC	Severe Hypoplasia and Dysplasia	Severe pons hypoplasia	N/A	<3rd p	N/A	This series
LIS_TUB_004_ fœtus08	TUBA1A	M	c.978A > C	p.K326N	23	Thick 2-layered cortex	-	+	+	N	+	Hypoplasic	c.ACC	Severe Hypoplasia and Dysplasia	Severe pons hypoplasia	-	<3rd p	Microretrognatism	This series
LIS_TUB_004_ fœtus08	TUBA1A	M	c.978A > C	p.K326N	23	Thick 2-layered cortex	-	+	+	N	+	Hypoplasic	c.ACC	Severe Hypoplasia and Dysplasia	Absent CST	-	<3rd p	Microretrognatism	This series
LIS_TUB_006_ fœtus04	TUBA1A	M	c.856C > T	p.L286F	23	Poorly differentiated CP (2–3 layers poorly individualized)	-	-	+	N	+	Hypoplasic	c.ACC	Moderate Hypoplasia	Severe pons hypoplasia	-	<3rd p	Hypoplastic external genital organs	[32]
LIS_TUB_006_ fœtus04	TUBA1A	M	c.856C > T	p.L286F	23	Poorly differentiated CP (2–3 layers poorly individualized)	-	-	+	N	+	Hypoplasic	c.ACC	Moderate Hypoplasia	Severe hypoplasia of the CST	-	<3rd p	Hypoplastic external genital organs	[32]
LIS_TUB_080_ fœtus24	TUBA1A	F	c.1112 T > A	p.V371E	23,3	Poorly differentiated CP (2–3 layers poorly individualized)	-	-	N/A	Non individualized	+	-	c.ACC	Severe Hypoplasia	Severe pons hypoplasia with hypoplasic olivary nuclei	-	<3rd p	Microretrognatism	This series
LIS_TUB_080_ fœtus24	TUBA1A	F	c.1112 T > A	p.V371E	23,3	Poorly differentiated CP (2–3 layers poorly individualized)	-	-	N/A	Non individualized	+	-	c.ACC	Severe Hypoplasia	Severe hypoplasia and Disorganization of the CST	-	<3rd p	Microretrognatism	This series
LIS_TUB_002_ fœtus20	TUBA1A	F	c.790C > T	p.R264H	24	Absent CP (2 layers including molecular layer)	-	Radial columnar heterotopic neurons	+	N	+	+	c.ACC	Moderate Hypoplasia	Severe pons hypoplasia with fragmented olivary nuclei	-	<3rd p	Microretrognatism
LIS_TUB_002_ fœtus20	TUBA1A	F	c.790C > T	p.R264H	24	Absent CP (2 layers including molecular layer)	-	Radial columnar heterotopic neurons	+	N	+	+	c.ACC	Moderate Hypoplasia	Severe hypoplasia and Disorganization of the CST	-	<3rd p	Microretrognatism
LIS_TUB_003_ fœtus18	TUBA1A	M	c.167 C > T	p. T56M	24,3	Absent CP (2 layers including molecular layer)	-	+	-	Non individualized	+	Hypoplasic	c.ACC	Severe Hypoplasia	Severe pons hypoplasia with hypoplasic olivary nuclei	Optic Nerve Hypoplasia	<3rd p	Microretrognatism	This series
LIS_TUB_003_ fœtus18	TUBA1A	M	c.167 C > T	p. T56M	24,3	Absent CP (2 layers including molecular layer)	-	+	-	Non individualized	+	Hypoplasic	c.ACC	Severe Hypoplasia	Severe hypoplasia and Disorganization of the CST	Optic Nerve Hypoplasia	<3rd p	Microretrognatism	This series
LIS_TUB_004_ fœtus09	TUBA1A	F	c.1285G > C	p.E429Q	25	4 layered cortex	-	Radial columnar heterotopic neurons	-	Non individualized	+	Hypoplasic	c.ACC	Severe Hypoplasia	Severe pons hypoplasia with hypoplasic olivary nuclei	-	<3rd p	Microretrognatism/dysmorphy/Exophthalmia/Hypertelorism	This series
LIS_TUB_004_ fœtus09	TUBA1A	F	c.1285G > C	p.E429Q	25	4 layered cortex	-	Radial columnar heterotopic neurons	-	Non individualized	+	Hypoplasic	c.ACC	Severe Hypoplasia	Severe hypoplasia and Disorganization of the CST	-	<3rd p	Microretrognatism/dysmorphy/Exophthalmia/Hypertelorism	This series
LIS_TUB_005_foetus01	TUBA1A	M	c.959G > A	p.R320H	25	Absent CP	Focal	Radial columnar heterotopic neurons	-	Non individualized	+	-	p.ACC	Severe Hypoplasia and Dysplasia	Severe hypoplasia (neuronal overmigration)-spinal cord anterior horn hypoplasia	N/A	<3rd p	Microretrognatism/dysmorphy/Exophthalmia/Hypertelorism	This series
LIS_TUB_005_foetus01	TUBA1A	M	c.959G > A	p.R320H	25	Absent CP	Focal	Radial columnar heterotopic neurons	-	Non individualized	+	-	p.ACC	Severe Hypoplasia and Dysplasia	Absent CST	N/A	<3rd p	Microretrognatism/dysmorphy/Exophthalmia/Hypertelorism	This series
LIS_TUB_079_ fœtus25	TUBA1A	M	c.302A > G	p.N101S	25	Poorly differentiated CP (2–3 layers poorly individualized)	-	Dispersed heterotopic neurons	+	Non individualized	N/A	-	c.ACC	Severe Hypoplasia and Dysplasia	Severe pons hypoplasia with hypoplasic olivary nuclei	-	<3rd p	Microretrognatism/dysmorphy/Exophthalmia/Hypertelorism	This series
LIS_TUB_079_ fœtus25	TUBA1A	M	c.302A > G	p.N101S	25	Poorly differentiated CP (2–3 layers poorly individualized)	-	Dispersed heterotopic neurons	+	Non individualized	N/A	-	c.ACC	Severe Hypoplasia and Dysplasia	Severe hypoplasia and Disorganization of the CST	-	<3rd p	Microretrognatism/dysmorphy/Exophthalmia/Hypertelorism	This series
LIS_TUB_009_ fœtus19	TUBB2B	M	c.745G > C	p.D294H	27	Absent CP (2 layers including molecular layer)	Massive -	-	-	Non individualized	+	-	c.ACC	Severe Hypoplasia	Severe hypoplasia with focal overmigration	N/A	<3rd p	Absent	This series
LIS_TUB_009_ fœtus19	TUBB2B	M	c.745G > C	p.D294H	27	Absent CP (2 layers including molecular layer)	Massive -	-	-	Non individualized	+	-	c.ACC	Severe Hypoplasia	Absent CST	N/A	<3rd p	Absent	This series
LIS_TUB_010_ fœtus17	TUBB3	M	c.1162A > G	p.M388V	27	Thin CP with 2 layers	-	Dispersed heterotopic neurons	+	N	+	Hypoplasic	c.ACC	Severe Hypoplasia and Dysplasia	Severe pons hypoplasia	Optic Nerve Hypoplasia	<3rd p	Absent	[33]
LIS_TUB_010_ fœtus17	TUBB3	M	c.1162A > G	p.M388V	27	Thin CP with 2 layers	-	Dispersed heterotopic neurons	+	N	+	Hypoplasic	c.ACC	Severe Hypoplasia and Dysplasia	Severe hypoplasia of the CST	Optic Nerve Hypoplasia	<3rd p	Absent	[33]
LIS_TUB_006_ fœtus03	TUBA1A	F	c.908 T > G	p.V303G	36	Thick severe 2 layered	-	-	-	N	+	Hypoplasic	p.ACC	Severe Hypoplasia and Dysplasia	Severe pons hypoplasia	-	<3rd p	Absent	[33]
LIS_TUB_006_ fœtus03	TUBA1A	F	c.908 T > G	p.V303G	36	Thick severe 2 layered	-	-	-	N	+	Hypoplasic	p.ACC	Severe Hypoplasia and Dysplasia	Severe hypoplasia of the CST	-	<3rd p	Absent	[33]
LIS_TUB_081_ fœtus26	TUBA1A	M	c.959G > A	p.R320H	26	Absent CP (2 layers including molecular layer)	-	Dispersed and nodular heterotopic neurons	N/A	N/A	-		c.ACC	Severe Hypoplasia and Dysplasia	Severe pons hypoplasia	-	<3rd p	Facial dysmorphism
LIS_TUB_081_ fœtus26	TUBA1A	M	c.959G > A	p.R320H	26	Absent CP (2 layers including molecular layer)	-	Dispersed and nodular heterotopic neurons	N/A	N/A	-		c.ACC	Severe Hypoplasia and Dysplasia	Severe hypoplasia of the CST	-	<3rd p	Facial dysmorphism

Abbreviations: TOP termination of the pregnancy, MicroLis microlissencephaly, N/A not available, ACC corpus callosum agenesis, GZ germinal zones, p. percentile; Foetal MRI based analysis of the phenotype; unilat: unilateral; +: Present; −: Absent; N: Normal; CP: cortical plate; CST: Corticospinal tract.

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ISSN: 2051-5960

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