Table 2.

Clinical characteristics of affected individuals with missense variants in GAS1

Individual	GAS1 variant		Inheritance	Other HPE-associated genes	Relevant clinical data	Reference
	Position	Change
10042	c.16C > G	p.Leu6Val	Paternal	SHH, SIX3, ZIC2 and TGIF are normal	Lobar HPE, hypotelorism, single nostril, cleft lip/palate. Father is phenotypically unaffected, mother described as having clear “microforms” of HPE	This study
9490	c.133C > G	p.Arg45Gly	Paternal	de novo ZIC2: c.994_1005dup, p. Cys335_Pro338dup; SHH, SIX3, TGIF are normal	Semilobar HPE, developmental delay, agenesis of the corpus callosum, microcephaly and spasticity	This study
Patient 1	c.599C > G	p.Thr200Arg	NA	SHH, SIX3, ZIC2 and TGIF are normal	Semilobar HPE, developmental delay, hypoplastic midface, upslanting palpebral fissures, proptosis, depressed nasal bridge, absent collumella, and bilateral cleft lip and palate	Ribeiro et al. (2010)
1024	c.660C > G	p.Asn220Lys	Paternal	ZIC2: c.709_711dup; p.His239dup (polymorphism); SHH, SIX3 and TGIF are normal	Hypoplastic corpus callosum, diabetes insipidus, craniosynostosis of metopic suture, pyriform apeture stenosis, midline cleft lip with complete premaxillary agenesis	This study
Patient 7	c.736G > T	p.Ala246Ser	NA	No data available	No data available	Ribeiro et al. (2010)
Patient 2	c.775G > A	p.Gly259Arg	NA	Normal karyotype, SHH, SIX3, TGIF, ZIC2 and GLI2 are normal	Hypotelorism, with proptosis, hypoplastic midface, depressed nasal bridge, absent collumella with notching of the tip, bilateral cleft lip and palate	Ribeiro et al. (2010)
Patient 3	c.808G > T	p.Asp270Tyr	NA	Paternally inherited SHH: c.653T > C, p.Leu218Pro; SIX3, ZIC2, TGIF and GLI2 are normal	Microcephaly, hypotelorism, hypoplastic midface, depressed nasal bridge and nasal bones, right cleft lip and palate, no brain structural anomalies	Ribeiro et al. (2010)
Patient 4	c.863A > G	p.Asp288Gly	de novo	de novo SHH: c.1088G > A, p.Cys363Tyr	Microcephaly, hypotelorism, midface hypoplasia, hypoplastic nasal bones, depressed nasal bridge, midline cleft lip and palate	Ribeiro et al. (2010)
6386	c.928C > T	p.Pro310Ser	Paternal	SHH, SIX3, ZIC2 and TGIF are normal	Semilobar HPE, absent pituitary and olfactory bulbs, microcephaly, hypotelorism, midface hypoplasia, depressed nasal bridge and hypoplastic septum, midline cleft lip with intact palate, micropenis	This study
4953	c.958G > T	p.Gly320Cys	Mother is normal; father is unavailable	ZIC2: c.709_711dup; p.His239dup (polymorphism); SHH, SIX3 and TGIF: are normal	HPE, no further clinical data available	This study