Phenotypic Spectrum of <i>COL4A1</i> Mutations: Porencephaly to Schizencephaly

Yoneda, Yuriko; Haginoya, Kazuhiro; Kato, Mitsuhiro; Osaka, Hitoshi; Yokochi, Kenji; Arai, Hiroshi; Kakita, Akiyoshi; Yamamoto, Takamichi; Otsuki, Yoshiro; Shimizu, Satoru; Wada, Takahito; Koyama, Norihisa; Mino, Yoichi; Kondo, Noriko; Takahashi, Satoru; Hirabayashi, Shinichi; Takanashi, Jun‐ichi; Okumura, Akihisa; Kumagai, Toshiyuki; Hirai, Satori; Nabetani, Makoto; Saitoh, Shinji; Hattori, Ayako; Yamasaki, Mami; Kumakura, Akira; Sugo, Yoshinobu; Nishiyama, Kiyomi; Miyatake, Satoko; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Matsumoto, Naomichi; Saitsu, Hirotomo

doi:10.1002/ana.23736

Cited by 151 publications

(127 citation statements)

References 30 publications

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“…All these patients had additional features including focal cortical dysplasia, intracranial calcification, hemolytic anemia, elevated creatine kinase, myopathy, ophthalmological features, or hematuria. 39 A complication of the hemorrhage can be the development of secondary hydrocephalus, as seen in patient D-II.1 and previously reported. 13,15,45 sporadic extensive bilateral porencephaly resembling hydranencephaly…”

Section: Prenatal and Neonatal Intracerebral Hemorrhage And Porencephalymentioning

confidence: 58%

“…For this, a PubMed search was performed, identifying 27 articles with clinical and mutation data on COL4A1 7,8,[10][11][12][13][14][15][16][17][18][19][20][21][22][29][30][31][32][33][34][35][36][37][38][39][40] and 3 articles with data on COL4A2 mutations. [26][27][28] A total of 137 individuals with a COL4A1 mutation from 60 families and 15 individuals with a COL4A2 mutation from 7 families have been reported.…”

Section: Methodsmentioning

confidence: 99%

“…Although cortical lesions secondary to tissue necrosis have been described in COL4A1 mutations, 15 malformations of the cortex, in particular schizencephaly, have only been appreciated recently as being associated with COL4A1 mutations, 37,39 Schizencephaly is defined as a cleft extending from the pial surface to the lateral ventricle, lined by heterotopic gray matter. 44 …”

Section: Cortical Malformations: Schizencephalymentioning

confidence: 99%

“…Porencephaly is one of the most frequently reported findings, described in 53 patients with COL4A1 mutations 7,8,12,14,15,17,18,21,[37][38][39] and 6 patients with COL4A2 mutation 27,28 ( Table 2). Because porencephaly was the first reported associated phenotype, however, there may be a bias in the inclusion of patients for COL4A1 and COL4A2 testing.…”

Section: Prenatal and Neonatal Intracerebral Hemorrhage And Porencephalymentioning

confidence: 99%

“…14,33,37,39,46 The diagnosis in patients with this PVL phenotype without a contributing family history or additional findings could easily be missed. Associated features, such as elevated creatine kinase concentration or microbleeds, may help in suspecting the diagnosis in the absence of other major findings such as porencephaly.…”

Section: Pvl With Intracranial Calcificationmentioning

confidence: 99%

See 4 more Smart Citations

The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature

Meuwissen

Halley

Smit

et al. 2015

Genetics in Medicine

220

234

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Section: Prenatal and Neonatal Intracerebral Hemorrhage And Porencephalymentioning

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Section: Cortical Malformations: Schizencephalymentioning

confidence: 99%

Section: Prenatal and Neonatal Intracerebral Hemorrhage And Porencephalymentioning

confidence: 99%

Section: Pvl With Intracranial Calcificationmentioning

confidence: 99%

See 3 more Smart Citations

The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature

Meuwissen

Halley

Smit

et al. 2015

Genetics in Medicine

220

234

View full text Add to dashboard Cite

Brain Calcifications in Adult-Onset Genetic Leukoencephalopathies

et al. 2017

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IMPORTANCE Adult-onset genetic leukoencephalopathies and leukodystrophies are increasingly recognized as a heterogeneous group of disorders with new diagnostic approaches and potential treatments. In the new era of genomics, the challenging interpretation of individual genetic variations requires an accurate phenotypic description and classification. Clinical and magnetic resonance imaging (MRI)-based approaches have been proposed to improve the diagnostic process of adult-onset leukoencephalopathies. Cerebral calcifications, when associated with white matter hyperintensities, are of major importance in the decision-making process to focus the diagnosis among the diversity of rare causes.OBSERVATIONS This literature review demonstrated that the morphologic features and topography of the calcifications observed in a careful combined analysis of computed tomographic and MRI scans may help indicate the diagnosis of adult-onset genetic leukoencephalopathies. Vascular genetic leukoencephalopathies are an important cause of leukoencephalopathy with calcifications. Among them, COL4A1-related disorders are frequently associated with spotlike calcifications in the basal ganglia. Adult-onset leukoencephalopathy with axonal spheroids, a probably underestimated disorder, is associated with a specific pattern of calcifications: small, symmetric, sparing the basal ganglia, and a stepping stone appearance in the frontal pericallosal region. Moreover, disorders primarily associated with basal ganglia calcifications, such as primary familial brain calcifications, can be associated with marked leukoencephalopathy. CONCLUSIONS AND RELEVANCEThe number of identified causes of adult-onset genetic leukoencephalopathies has recently increased. A diagnostic algorithm should take into account the pattern of calcifications to better target the genetic analyses.

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Prevalence of Pathogenic Copy Number Variation in Adults With Pediatric-Onset Epilepsy and Intellectual Disability

et al. 2017

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IMPORTANCECopy number variation (CNV) is an important cause of neuropsychiatric disorders. Little is known about the role of CNV in adults with epilepsy and intellectual disability.OBJECTIVES To evaluate the prevalence of pathogenic CNVs and identify possible candidate CNVs and genes in patients with epilepsy and intellectual disability. DESIGN, SETTING, AND PARTICIPANTSIn this cross-sectional study, genome-wide microarray was used to evaluate a cohort of 143 adults with unexplained childhood-onset epilepsy and intellectual disability who were recruited from the Toronto Western Hospital epilepsy outpatient clinic from January 1, 2012, through December 31, 2014. The inclusion criteria were (1) pediatric seizure onset with ongoing seizure activity in adulthood, (2) intellectual disability of any degree, and (3) no structural brain abnormalities or metabolic conditions that could explain the seizures.MAIN OUTCOMES AND MEASURES DNA screening was performed using genome-wide microarray platforms. Pathogenicity of CNVs was assessed based on the American College of Medical Genetics guidelines. The Residual Variation Intolerance Score was used to evaluate genes within the identified CNVs that could play a role in each patient's phenotype. RESULTSOf the 2335 patients, 143 probands were investigated (mean [SD] age, 24.6 [10.8] years; 69 male and 74 female). Twenty-three probands (16.1%) and 4 affected relatives (2.8%) (mean [SD] age, 24.1 [6.1] years; 11 male and 16 female) presented with pathogenic or likely pathogenic CNVs (0.08-18.9 Mb). Five of the 23 probands with positive results (21.7%) had more than 1 CNV reported. Parental testing revealed de novo CNVs in 11 (47.8%), with CNVs inherited from a parent in 4 probands (17.4%). Sixteen of 23 probands (69.6%) presented with previously cataloged human genetic disorders and/or defined CNV hot spots in epilepsy. Eight nonrecurrent rare CNVs that overlapped 1 or more genes associated with intellectual disability, autism, and/or epilepsy were identified: 2p16.1-p15 duplication, 6p25.3-p25.1 duplication, 8p23.3p23.1 deletion, 9p24.3-p23 deletion, 10q11.22-q11.23 duplication, 12p13.33-13.2 duplication, 13q34 deletion, and 16p13.2 duplication. Five genes are of particular interest given their potential pathogenicity in the corresponding phenotypes and least tolerability to variation: ABAT, KIAA2022, COL4A1, CACNA1C, and SMARCA2. ABAT duplication was associated with Lennox-Gastaut syndrome and KIAA2022 deletion with Jeavons syndrome. CONCLUSIONS AND RELEVANCEThe high prevalence of pathogenic CNVs in this study highlights the importance of microarray analysis in adults with unexplained childhood-onset epilepsy and intellectual disability. Additional studies and comparison with similar cases are required to evaluate the effects of deletions and duplications that overlap specific genes.

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Phenotypic Spectrum of COL4A1 Mutations: Porencephaly to Schizencephaly

Cited by 151 publications

References 30 publications

The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature

The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature

Brain Calcifications in Adult-Onset Genetic Leukoencephalopathies

Prevalence of Pathogenic Copy Number Variation in Adults With Pediatric-Onset Epilepsy and Intellectual Disability

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