#300868
Table of Contents
Alternative titles; symbols
| Location | Phenotype | Inheritance |
Phenotype mapping key |
Phenotype MIM number |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 16p13.3 | Multiple congenital anomalies-hypotonia-seizures syndrome 4 | AR | 3 | 618548 | PIGQ | 605754 |
| 18q21.33 | Multiple congenital anomalies-hypotonia-seizures syndrome 1 | AR | 3 | 614080 | PIGN | 606097 |
| 20q13.12 | Multiple congenital anomalies-hypotonia-seizures syndrome 3 | AR | 3 | 615398 | PIGT | 610272 |
| Xp22.2 | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | XLR | 3 | 300868 | PIGA | 311770 |
A number sign (#) is used with this entry because multiple congenital anomalies-hypotonia-seizures syndrome-2 (MCAHS2) is caused by mutation in the PIGA gene (311770) on chromosome Xp22.
Multiple congenital anomalies-hypotonia-seizures syndrome-2 (MCAHS2) is an X-linked recessive neurodevelopmental disorder characterized by dysmorphic features, neonatal hypotonia, early-onset myoclonic seizures, and variable congenital anomalies involving the central nervous, cardiac, and urinary systems. Some affected individuals die in infancy (summary by Johnston et al., 2012). The phenotype shows clinical variability with regard to severity and extraneurologic features. However, most patients present in infancy with early-onset epileptic encephalopathy associated with developmental arrest and subsequent severe neurologic disability; these features are consistent with a form of developmental and epileptic encephalopathy (DEE) (summary by Belet et al., 2014, Kato et al., 2014). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis.
For a discussion of genetic heterogeneity of MCAHS, see MCAHS1 (614080).
For a discussion of nomenclature and genetic heterogeneity of DEE, see 308350.
For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Johnston et al. (2012) reported a family in which 2 brothers had a lethal multiple congenital anomaly disorder. Both infants were born by cesarean section due to breech presentation and were noted to have large size at birth. Both infants developed severe myoclonic seizures associated with a burst-suppression pattern on EEG in the first weeks of life; they died at 10 and 11 weeks of age. The first-born boy had Pierre-Robin sequence, a prominent occiput, enlarged fontanel, depressed nasal bridge, short, anteverted nose, malar flattening, upslanted palpebral fissures, overfolded helix, small mouth with downturned corners, and short neck. He had joint contractures, small nails, broad palms with short fingers, and hypotonia. Brain MRI showed thin corpus callosum, white matter immaturity, no septum pellucidum, and cerebellar hypoplasia. Other features included systolic murmur, atrial septal defect, obstructive apnea, vesicoureteral reflux, and a duplicated collecting system. He died of pneumonia at age 11 weeks. His brother had similar dysmorphic features, with the addition of a fused metopic suture and high-arched palate. He also had hypotonia, hyperreflexia, contractures, myoclonic seizures, and small patent ductus arteriosus. He died of respiratory failure at age 10 weeks. Postmortem examination showed thin corpus callosum, cerebellar hypoplasia, lack of the olfactory bulb and tracts, abnormal cortical lamination, and dysplastic pons. The diagnosis was hypoxic ischemic encephalopathy and brain malformation with arhinencephaly. Neither patient had evidence of hemolytic anemia or clinical hemoglobinuria, although 1 had low serum calcium and the other had increased serum alkaline phosphatase. A maternal uncle reportedly died of a 'stroke' at age 1 month.
Belet et al. (2014) reported a large Belgian family in which 5 males had profound developmental retardation, axial hypotonia, infantile seizures, and hypsarrhythmia on EEG. The family was previously reported as having West syndrome by Claes et al. (1997) (family B). The patients had onset of severe infantile spasms, including myoclonic and generalized seizures, between 5 and 6 months of age. All had complete arrest of psychomotor development after seizure onset, and 4 patients died as children or young adults. Neuropathology of 1 patient showed cortical and cerebellar atrophy, neuronal loss, and gliosis and microspongiosis. Female family members were unaffected.
Kato et al. (2014) reported 5 patients from 4 Japanese families with MCAHS2 manifest as early-onset epileptic encephalopathy. One of the patients had been diagnosed clinically with Schinzel-Giedion syndrome (269150) (Watanabe et al., 2012). Onset of tonic or myoclonic seizures occurred between 1 and 7 months of age, and were refractory in most patients. All had profound intellectual disability, 3 were bedridden with severe motor disturbances, and 2 brothers had a slightly less severe phenotype with no motor disturbances. EEG in the most severe cases showed hypsarrhythmia or burst-suppression pattern. The 3 most severely affected patients had dysmorphic facial features including depressed nasal bridge, short anteverted nose, downturned corners of the mouth, and high-arched palate. Brain MRI of these patients showed cortical atrophy, thin corpus callosum, delayed myelination, and deep white-matter signal abnormalities. One patient had vesicoureteral reflux, 2 had hypotonia, and 2 had joint contractures. Two patients had increased serum alkaline phosphatase. Flow cytometric analysis of patient granulocytes showed decreased expression of the glycosylphosphatidylinositol (GPI)-anchored protein CD16 (see 146740); unaffected carrier mothers showed less severely decreased expression of CD16 on granulocytes.
Van der Crabben et al. (2014) reported a boy with MCAHS2. He had delayed psychomotor development with axial hypotonia and developed refractory seizures at 8.5 months of age. He subsequently showed developmental regression with an encephalopathic phenotype. Other features included atrial septal defect and mild dysmorphic features, such as high anterior hairline, upslanting palpebral fissures, thin vermilion, long philtrum, alveolar ridge overgrowth, and absence of teeth. He also had obesity and accelerated linear growth. Brain MRI showed progressive cerebral atrophy, thin corpus callosum, and insufficient myelination. Laboratory studies showed fluctuating elevated alkaline phosphatase levels. The child died of cardiorespiratory arrest at age 2.5 years.
Terespolsky et al. (1995) reported a family in which 4 maternally related male cousins were born with multiple congenital anomalies. One fetus was voluntarily aborted at 19 weeks' gestation, after multicystic kidneys were detected on ultrasound; the remaining 3 all died within the first 8 weeks of life from pneumonia or sepsis. The 3 liveborn males were hydropic at birth and had a combination of craniofacial anomalies including macrocephaly; apparently low-set posteriorly angulated ears; hypertelorism; short, broad nose with anteverted nares; large mouth with a thin vermilion upper border; prominent philtrum; high-arched or cleft palate; short neck; redundant skin; and hypoplastic nails; skeletal defects involving the upper and lower limbs; and gastrointestinal and genitourinary anomalies. All 3 patients were hypotonic and neurologically impaired from birth. With the exception of a trilobate left lung in 1 patient, the cardiorespiratory system was structurally normal. Terespolsky et al. (1995) suggested that the patients had a severe form of Simpson-Golabi-Behmel syndrome (see SGBS1, 312870). In a follow-up of the affected fetus from the family originally reported by Terespolsky et al. (1995), Fauth et al. (2016) reported that the pregnancy was terminated at 19 weeks' gestation after multiple congenital anomalies were found on prenatal imaging. Fauth et al. (2016) detected a mutation in the PIGA gene in this patient (see MOLECULAR GENETICS).
Fauth et al. (2016) reported 3 male patients from 2 unrelated families with a lethal multiple congenital anomaly syndrome. One died at age 15 days, 1 died at age 3 months, and the third died in utero. A pregnancy in each family was complicated by polyhydramnios, and 2 of the patients had somatic overgrowth. Two patients had severe hypotonia and neonatal onset of seizures with a burst-suppression pattern on EEG, consistent with Ohtahara syndrome. Dysmorphic facial features included coarse facies, high anterior hairline, upslanted palpebral fissures, depressed nasal bridge with short nose and anteverted nares, retrognathia, and short webbed neck. Other common features included joint contractures, short limbs, short distal phalanges, and small penis. One patient had a small cerebellum with white matter immaturity and small optic nerves, whereas the other had a smooth gyration pattern. One of the patients had mildly increased serum alkaline phosphatase.
The transmission pattern of the disorder in the family reported by Johnston et al. (2012) was consistent with X-linked recessive inheritance.
In the family reported by Terespolsky et al. (1995), Brzustowicz et al. (1999) mapped the locus for the disorder to a 6-Mb region on chromosome Xp22 (maximum lod score of 3.31), which they called 'SBGS2' (see 300209). The findings excluded involvement of the glypican-3 gene (GPC3; 300037), which is responsible for SGBS1 and maps to Xq26.
By exome sequencing of the X chromosome in a family with multiple congenital anomalies-hypotonia-seizures syndrome-2, Johnston et al. (2012) identified a germline mutation in the PIGA gene (R412X; 311770.0011). Two affected boys carried the mutation, and 2 obligate female carriers were heterozygous for the mutation; both female carriers showed 100% skewed X inactivation. In vitro functional expression studies in PIGA-null cell lines showed that the R412X mutant protein retained some residual activity with partial restoration of GPI-anchored proteins, suggesting that it is not a null allele. The findings indicated that GPI anchors are important for normal development, particularly of the central nervous system.
In 1 of the patients from the family reported by Claes et al. (1997), Belet et al. (2014) identified a hemizygous truncating mutation in the PIGA gene (311770.0012). The mutation, which was found by X-exome sequencing and confirmed by Sanger sequencing, was not found in 4 healthy males and was present in the unaffected mother of the proband, the unaffected grandmother, and a maternal aunt. DNA was not available from the 4 deceased affected family members.
In 5 boys from 4 unrelated Japanese families with MCAHS2 manifest as early-onset epileptic encephalopathy, Kato et al. (2014) identified hemizygous mutations in the PIGA gene (see, e.g., 311770.0011; 311770.0013-311770.0015). The mutations were found by whole-exome sequencing. In vitro functional expression studies showed a variable loss of PIGA activity, with a correlation between severity of phenotype and degree of residual enzymatic activity.
In a boy with MCAHS2, van der Crabben et al. (2014) identified a hemizygous mutation in the PIGA gene (311770.0017).
In 4 male patients from 3 unrelated families with MCAHS2, including the family originally reported by Terespolsky et al. (1995) as Simpson-Golabi-Behmel syndrome (see SGBS2, 300209), Fauth et al. (2016) identified the same hemizygous truncating mutation in the PIGA gene (R412X; 311770.0011). The mutation was found in the heterozygous state in the 2 clinically unaffected mothers who were tested.
Belet, S., Fieremans, N., Yuan, X., Van Esch, H., Verbeeck, J., Ye, Z., Cheng, L., Brodsky, B. R., Hu, H., Kalscheuer, V. M., Brodsky, R. A., Froyen, G. Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality. Hum. Mutat. 35: 350-355, 2014. [PubMed: 24357517, related citations] [Full Text]
Brzustowicz, L. M., Farrell, S., Khan, M. B., Weksberg, R. Mapping of a new SGBS locus to chromosome Xp22 in a family with a severe form of Simpson-Golabi-Behmel syndrome. Am. J. Hum. Genet. 65: 779-783, 1999. [PubMed: 10441586, related citations] [Full Text]
Claes, S., Devriendt, K., Lagae, L., Ceulemans, B., Dom, L., Casaer, P., Raeymaekers, P., Cassiman, J. J., Fryns, J. P. The X-linked infantile spasms syndrome (MIM 308350) maps to Xp11.4-Xpter in two pedigrees. Ann. Neurol. 42: 360-364, 1997. [PubMed: 9307258, related citations] [Full Text]
Fauth, C., Steindl, K., Toutain, A., Farrell, S., Witsch-Baumgartner, M., Karall, D., Joset, P., Bohm, S., Baumer, A., Maier, O., Zschocke, J., Weksberg, R., Marshall, C. R., Rauch, A. A recurrent germline mutation in the PIGA gene causes Simpson-Golabi-Behmel syndrome type 2. Am. J. Med. Genet. 170A: 392-402, 2016. [PubMed: 26545172, related citations] [Full Text]
Johnston, J. J., Gropman, A. L., Sapp, J. C., Teer, J. K., Martin, J. M., Liu, C. F., Yuan, X., Ye, Z., Cheng, L., Brodsky, R. A., Biesecker, L. G. The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria. Am. J. Hum. Genet. 90: 295-300, 2012. [PubMed: 22305531, images, related citations] [Full Text]
Kato, M., Saitsu, H., Murakami, Y., Kikuchi, K., Watanabe, S., Iai, M., Miya, K, Matsuura, R., Takayama, R., Ohba, C., Nakashima, M., Tsurusaki, Y., Miyake, N., Hamano, S., Osaka, H., Hayasaka, K., Kinoshita, T., Matsumoto, N. PIGA mutations cause early-onset epileptic encephalopathies and distinctive features. Neurology 82: 1587-1596, 2014. [PubMed: 24706016, related citations] [Full Text]
Terespolsky, D., Farrell, S. A., Siegel-Bartelt, J., Weksberg, R. Infantile lethal variant of Simpson-Golabi-Behmel syndrome associated with hydrops fetalis. Am. J. Med. Genet. 59: 329-333, 1995. [PubMed: 8599356, related citations] [Full Text]
van der Crabben, S. N., Harakalova, M., Brilstra, E. H., van Berkestijn, F. M. C., Hofstede, F. C., van Vught, A. J., Cuppen, E., Kloosterman, W., Ploos van Amstel, H. K., van Haaften, G., van Haelst, M. M. Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities. Am. J. Med. Genet. 164A: 29-35, 2014. [PubMed: 24259184, related citations] [Full Text]
Watanabe, S., Murayama, A., Haginoya, K., Tanaka, S., Togashi, N., Abukawa, D., Sato, A., Imaizumi, M., Yoshikawa, H., Takayama, R., Wakusawa, K., Kobayashi, S., Sato, I., Onuma, A. Schinzel-Giedion syndrome: a further cause of early myoclonic encephalopathy and vacuolating myelinopathy. Brain Dev. 34: 151-155, 2012. [PubMed: 21507589, related citations] [Full Text]
Alternative titles; symbols
ORPHA: 300496; DO: 0080139;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xp22.2 | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 300868 | X-linked recessive | 3 | PIGA | 311770 |
A number sign (#) is used with this entry because multiple congenital anomalies-hypotonia-seizures syndrome-2 (MCAHS2) is caused by mutation in the PIGA gene (311770) on chromosome Xp22.
Multiple congenital anomalies-hypotonia-seizures syndrome-2 (MCAHS2) is an X-linked recessive neurodevelopmental disorder characterized by dysmorphic features, neonatal hypotonia, early-onset myoclonic seizures, and variable congenital anomalies involving the central nervous, cardiac, and urinary systems. Some affected individuals die in infancy (summary by Johnston et al., 2012). The phenotype shows clinical variability with regard to severity and extraneurologic features. However, most patients present in infancy with early-onset epileptic encephalopathy associated with developmental arrest and subsequent severe neurologic disability; these features are consistent with a form of developmental and epileptic encephalopathy (DEE) (summary by Belet et al., 2014, Kato et al., 2014). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis.
For a discussion of genetic heterogeneity of MCAHS, see MCAHS1 (614080).
For a discussion of nomenclature and genetic heterogeneity of DEE, see 308350.
For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Johnston et al. (2012) reported a family in which 2 brothers had a lethal multiple congenital anomaly disorder. Both infants were born by cesarean section due to breech presentation and were noted to have large size at birth. Both infants developed severe myoclonic seizures associated with a burst-suppression pattern on EEG in the first weeks of life; they died at 10 and 11 weeks of age. The first-born boy had Pierre-Robin sequence, a prominent occiput, enlarged fontanel, depressed nasal bridge, short, anteverted nose, malar flattening, upslanted palpebral fissures, overfolded helix, small mouth with downturned corners, and short neck. He had joint contractures, small nails, broad palms with short fingers, and hypotonia. Brain MRI showed thin corpus callosum, white matter immaturity, no septum pellucidum, and cerebellar hypoplasia. Other features included systolic murmur, atrial septal defect, obstructive apnea, vesicoureteral reflux, and a duplicated collecting system. He died of pneumonia at age 11 weeks. His brother had similar dysmorphic features, with the addition of a fused metopic suture and high-arched palate. He also had hypotonia, hyperreflexia, contractures, myoclonic seizures, and small patent ductus arteriosus. He died of respiratory failure at age 10 weeks. Postmortem examination showed thin corpus callosum, cerebellar hypoplasia, lack of the olfactory bulb and tracts, abnormal cortical lamination, and dysplastic pons. The diagnosis was hypoxic ischemic encephalopathy and brain malformation with arhinencephaly. Neither patient had evidence of hemolytic anemia or clinical hemoglobinuria, although 1 had low serum calcium and the other had increased serum alkaline phosphatase. A maternal uncle reportedly died of a 'stroke' at age 1 month.
Belet et al. (2014) reported a large Belgian family in which 5 males had profound developmental retardation, axial hypotonia, infantile seizures, and hypsarrhythmia on EEG. The family was previously reported as having West syndrome by Claes et al. (1997) (family B). The patients had onset of severe infantile spasms, including myoclonic and generalized seizures, between 5 and 6 months of age. All had complete arrest of psychomotor development after seizure onset, and 4 patients died as children or young adults. Neuropathology of 1 patient showed cortical and cerebellar atrophy, neuronal loss, and gliosis and microspongiosis. Female family members were unaffected.
Kato et al. (2014) reported 5 patients from 4 Japanese families with MCAHS2 manifest as early-onset epileptic encephalopathy. One of the patients had been diagnosed clinically with Schinzel-Giedion syndrome (269150) (Watanabe et al., 2012). Onset of tonic or myoclonic seizures occurred between 1 and 7 months of age, and were refractory in most patients. All had profound intellectual disability, 3 were bedridden with severe motor disturbances, and 2 brothers had a slightly less severe phenotype with no motor disturbances. EEG in the most severe cases showed hypsarrhythmia or burst-suppression pattern. The 3 most severely affected patients had dysmorphic facial features including depressed nasal bridge, short anteverted nose, downturned corners of the mouth, and high-arched palate. Brain MRI of these patients showed cortical atrophy, thin corpus callosum, delayed myelination, and deep white-matter signal abnormalities. One patient had vesicoureteral reflux, 2 had hypotonia, and 2 had joint contractures. Two patients had increased serum alkaline phosphatase. Flow cytometric analysis of patient granulocytes showed decreased expression of the glycosylphosphatidylinositol (GPI)-anchored protein CD16 (see 146740); unaffected carrier mothers showed less severely decreased expression of CD16 on granulocytes.
Van der Crabben et al. (2014) reported a boy with MCAHS2. He had delayed psychomotor development with axial hypotonia and developed refractory seizures at 8.5 months of age. He subsequently showed developmental regression with an encephalopathic phenotype. Other features included atrial septal defect and mild dysmorphic features, such as high anterior hairline, upslanting palpebral fissures, thin vermilion, long philtrum, alveolar ridge overgrowth, and absence of teeth. He also had obesity and accelerated linear growth. Brain MRI showed progressive cerebral atrophy, thin corpus callosum, and insufficient myelination. Laboratory studies showed fluctuating elevated alkaline phosphatase levels. The child died of cardiorespiratory arrest at age 2.5 years.
Terespolsky et al. (1995) reported a family in which 4 maternally related male cousins were born with multiple congenital anomalies. One fetus was voluntarily aborted at 19 weeks' gestation, after multicystic kidneys were detected on ultrasound; the remaining 3 all died within the first 8 weeks of life from pneumonia or sepsis. The 3 liveborn males were hydropic at birth and had a combination of craniofacial anomalies including macrocephaly; apparently low-set posteriorly angulated ears; hypertelorism; short, broad nose with anteverted nares; large mouth with a thin vermilion upper border; prominent philtrum; high-arched or cleft palate; short neck; redundant skin; and hypoplastic nails; skeletal defects involving the upper and lower limbs; and gastrointestinal and genitourinary anomalies. All 3 patients were hypotonic and neurologically impaired from birth. With the exception of a trilobate left lung in 1 patient, the cardiorespiratory system was structurally normal. Terespolsky et al. (1995) suggested that the patients had a severe form of Simpson-Golabi-Behmel syndrome (see SGBS1, 312870). In a follow-up of the affected fetus from the family originally reported by Terespolsky et al. (1995), Fauth et al. (2016) reported that the pregnancy was terminated at 19 weeks' gestation after multiple congenital anomalies were found on prenatal imaging. Fauth et al. (2016) detected a mutation in the PIGA gene in this patient (see MOLECULAR GENETICS).
Fauth et al. (2016) reported 3 male patients from 2 unrelated families with a lethal multiple congenital anomaly syndrome. One died at age 15 days, 1 died at age 3 months, and the third died in utero. A pregnancy in each family was complicated by polyhydramnios, and 2 of the patients had somatic overgrowth. Two patients had severe hypotonia and neonatal onset of seizures with a burst-suppression pattern on EEG, consistent with Ohtahara syndrome. Dysmorphic facial features included coarse facies, high anterior hairline, upslanted palpebral fissures, depressed nasal bridge with short nose and anteverted nares, retrognathia, and short webbed neck. Other common features included joint contractures, short limbs, short distal phalanges, and small penis. One patient had a small cerebellum with white matter immaturity and small optic nerves, whereas the other had a smooth gyration pattern. One of the patients had mildly increased serum alkaline phosphatase.
The transmission pattern of the disorder in the family reported by Johnston et al. (2012) was consistent with X-linked recessive inheritance.
In the family reported by Terespolsky et al. (1995), Brzustowicz et al. (1999) mapped the locus for the disorder to a 6-Mb region on chromosome Xp22 (maximum lod score of 3.31), which they called 'SBGS2' (see 300209). The findings excluded involvement of the glypican-3 gene (GPC3; 300037), which is responsible for SGBS1 and maps to Xq26.
By exome sequencing of the X chromosome in a family with multiple congenital anomalies-hypotonia-seizures syndrome-2, Johnston et al. (2012) identified a germline mutation in the PIGA gene (R412X; 311770.0011). Two affected boys carried the mutation, and 2 obligate female carriers were heterozygous for the mutation; both female carriers showed 100% skewed X inactivation. In vitro functional expression studies in PIGA-null cell lines showed that the R412X mutant protein retained some residual activity with partial restoration of GPI-anchored proteins, suggesting that it is not a null allele. The findings indicated that GPI anchors are important for normal development, particularly of the central nervous system.
In 1 of the patients from the family reported by Claes et al. (1997), Belet et al. (2014) identified a hemizygous truncating mutation in the PIGA gene (311770.0012). The mutation, which was found by X-exome sequencing and confirmed by Sanger sequencing, was not found in 4 healthy males and was present in the unaffected mother of the proband, the unaffected grandmother, and a maternal aunt. DNA was not available from the 4 deceased affected family members.
In 5 boys from 4 unrelated Japanese families with MCAHS2 manifest as early-onset epileptic encephalopathy, Kato et al. (2014) identified hemizygous mutations in the PIGA gene (see, e.g., 311770.0011; 311770.0013-311770.0015). The mutations were found by whole-exome sequencing. In vitro functional expression studies showed a variable loss of PIGA activity, with a correlation between severity of phenotype and degree of residual enzymatic activity.
In a boy with MCAHS2, van der Crabben et al. (2014) identified a hemizygous mutation in the PIGA gene (311770.0017).
In 4 male patients from 3 unrelated families with MCAHS2, including the family originally reported by Terespolsky et al. (1995) as Simpson-Golabi-Behmel syndrome (see SGBS2, 300209), Fauth et al. (2016) identified the same hemizygous truncating mutation in the PIGA gene (R412X; 311770.0011). The mutation was found in the heterozygous state in the 2 clinically unaffected mothers who were tested.
Belet, S., Fieremans, N., Yuan, X., Van Esch, H., Verbeeck, J., Ye, Z., Cheng, L., Brodsky, B. R., Hu, H., Kalscheuer, V. M., Brodsky, R. A., Froyen, G. Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality. Hum. Mutat. 35: 350-355, 2014. [PubMed: 24357517] [Full Text: https://doi.org/10.1002/humu.22498]
Brzustowicz, L. M., Farrell, S., Khan, M. B., Weksberg, R. Mapping of a new SGBS locus to chromosome Xp22 in a family with a severe form of Simpson-Golabi-Behmel syndrome. Am. J. Hum. Genet. 65: 779-783, 1999. [PubMed: 10441586] [Full Text: https://doi.org/10.1086/302527]
Claes, S., Devriendt, K., Lagae, L., Ceulemans, B., Dom, L., Casaer, P., Raeymaekers, P., Cassiman, J. J., Fryns, J. P. The X-linked infantile spasms syndrome (MIM 308350) maps to Xp11.4-Xpter in two pedigrees. Ann. Neurol. 42: 360-364, 1997. [PubMed: 9307258] [Full Text: https://doi.org/10.1002/ana.410420313]
Fauth, C., Steindl, K., Toutain, A., Farrell, S., Witsch-Baumgartner, M., Karall, D., Joset, P., Bohm, S., Baumer, A., Maier, O., Zschocke, J., Weksberg, R., Marshall, C. R., Rauch, A. A recurrent germline mutation in the PIGA gene causes Simpson-Golabi-Behmel syndrome type 2. Am. J. Med. Genet. 170A: 392-402, 2016. [PubMed: 26545172] [Full Text: https://doi.org/10.1002/ajmg.a.37452]
Johnston, J. J., Gropman, A. L., Sapp, J. C., Teer, J. K., Martin, J. M., Liu, C. F., Yuan, X., Ye, Z., Cheng, L., Brodsky, R. A., Biesecker, L. G. The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria. Am. J. Hum. Genet. 90: 295-300, 2012. [PubMed: 22305531] [Full Text: https://doi.org/10.1016/j.ajhg.2011.11.031]
Kato, M., Saitsu, H., Murakami, Y., Kikuchi, K., Watanabe, S., Iai, M., Miya, K, Matsuura, R., Takayama, R., Ohba, C., Nakashima, M., Tsurusaki, Y., Miyake, N., Hamano, S., Osaka, H., Hayasaka, K., Kinoshita, T., Matsumoto, N. PIGA mutations cause early-onset epileptic encephalopathies and distinctive features. Neurology 82: 1587-1596, 2014. [PubMed: 24706016] [Full Text: https://doi.org/10.1212/WNL.0000000000000389]
Terespolsky, D., Farrell, S. A., Siegel-Bartelt, J., Weksberg, R. Infantile lethal variant of Simpson-Golabi-Behmel syndrome associated with hydrops fetalis. Am. J. Med. Genet. 59: 329-333, 1995. [PubMed: 8599356] [Full Text: https://doi.org/10.1002/ajmg.1320590310]
van der Crabben, S. N., Harakalova, M., Brilstra, E. H., van Berkestijn, F. M. C., Hofstede, F. C., van Vught, A. J., Cuppen, E., Kloosterman, W., Ploos van Amstel, H. K., van Haaften, G., van Haelst, M. M. Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities. Am. J. Med. Genet. 164A: 29-35, 2014. [PubMed: 24259184] [Full Text: https://doi.org/10.1002/ajmg.a.36184]
Watanabe, S., Murayama, A., Haginoya, K., Tanaka, S., Togashi, N., Abukawa, D., Sato, A., Imaizumi, M., Yoshikawa, H., Takayama, R., Wakusawa, K., Kobayashi, S., Sato, I., Onuma, A. Schinzel-Giedion syndrome: a further cause of early myoclonic encephalopathy and vacuolating myelinopathy. Brain Dev. 34: 151-155, 2012. [PubMed: 21507589] [Full Text: https://doi.org/10.1016/j.braindev.2011.03.010]
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