Pediatrics InternationalVolume 53, Issue 1 p. 107-110 A case of progressive familial intrahepatic cholestasis type 1 with compound heterozygous mutations of ATP8B1 Chikahiko Numakura, Chikahiko Numakura Department of Pediatrics, Yamagata University School of Medicine, YamagataSearch for more papers by this authorDaiki Abukawa, Daiki Abukawa Department of General Pediatrics, Miyagi Children's Hospital, SendaiSearch for more papers by this authorToshiyuki Kimura, Toshiyuki Kimura Department of Pediatrics, Yamagata Prefectural and Sakata Municipal Hospital Organization, Sakata, JapanSearch for more papers by this authorSaori Tanabe, Saori Tanabe Department of Pediatrics, Yamagata Prefectural and Sakata Municipal Hospital Organization, Sakata, JapanSearch for more papers by this authorKiyoshi Hayasaka, Corresponding Author Kiyoshi Hayasaka Department of Pediatrics, Yamagata University School of Medicine, YamagataKiyoshi Hayasaka, MD, PhD, Department of Pediatrics, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan. Email: [email protected]Search for more papers by this author Chikahiko Numakura, Chikahiko Numakura Department of Pediatrics, Yamagata University School of Medicine, YamagataSearch for more papers by this authorDaiki Abukawa, Daiki Abukawa Department of General Pediatrics, Miyagi Children's Hospital, SendaiSearch for more papers by this authorToshiyuki Kimura, Toshiyuki Kimura Department of Pediatrics, Yamagata Prefectural and Sakata Municipal Hospital Organization, Sakata, JapanSearch for more papers by this authorSaori Tanabe, Saori Tanabe Department of Pediatrics, Yamagata Prefectural and Sakata Municipal Hospital Organization, Sakata, JapanSearch for more papers by this authorKiyoshi Hayasaka, Corresponding Author Kiyoshi Hayasaka Department of Pediatrics, Yamagata University School of Medicine, YamagataKiyoshi Hayasaka, MD, PhD, Department of Pediatrics, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan. Email: [email protected]Search for more papers by this author First published: 15 March 2011 https://doi.org/10.1111/j.1442-200X.2010.03238.xCitations: 5Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Bull LN, van Eijk MJ, Pawlikowska L et al. A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Nat. Genet. 1998; 18: 219–24. 2 Strautnieks SS, Bull LN, Knisely AS et al. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat. Genet. 1998; 20: 233–8. 3 de Vree JM, Jacquemin E, Sturm E et al. Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 282–7. 4 Klomp LW, Vargas JC, van Mil SW et al. Characterization of mutations in ATP8B1 associated with hereditary cholestasis. Hepatology 2004; 40: 27–38. 5 Crow JF. The origins, patterns and implications of human spontaneous mutation. Nat. Rev. Genet. 2000; 1: 40–7. 6 Paulusma CC, Folmer DE, Ho-Mok KS et al. ATP8B1 requires an accessory protein for endoplasmic reticulum exit and plasma membrane lipid flippase activity. Hepatology 2008; 47: 268–78. 7 Nagasaka H, Yorifuji T, Hirano K et al. Effects of bezafibrate on dyslipidemia with cholestasis in children with familial intrahepatic cholestasis-1 deficiency manifesting progressive familial intrahepatic cholestasis. Metabolism 2009; 58: 48–54. Citing Literature Volume53, Issue1February 2011Pages 107-110 ReferencesRelatedInformation

SOX2 anophthalmia syndrome characteristically presents as anophthalmia or microphthalmia, with various extraocular symptoms, such as hypogonadotropic hypogonadism, brain anomaly, and esophageal abnormalities. In this report, we describe a patient with SOX2 anophthalmia syndrome complicated with a dental anomaly, multiple supernumerary impacted teeth, and persistence of deciduous teeth. Multiple supernumerary teeth are usually not solitary symptoms, but indicate systemic syndrome such as cleidocranial dysplasia. In odontogenesis, many transcriptional factors, such as BMPs, FGFs, and Wnts, play significant roles and SOX2 is known to interact with some of them. The role of SOX2 in dental development remains unknown, however, multiple supernumerary teeth can be considered as extraocular symptoms of SOX2 anophthalmia syndrome, rather than the coincidence of two rare diseases. © 2010 Wiley‐Liss, Inc.

American Journal of Medical Genetics Part AVolume 152A, Issue 9 p. fm i-fm v Table of ContentsFree Access Table of Contents, Volume 152A, Number 9, September 2010 First published: 20 August 2010 https://doi.org/10.1002/ajmg.a.33697AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume152A, Issue9September 2010Pages fm i-fm v RelatedInformation

Propionic acidemia (PA) is an inborn error of organic acid metabolism caused by a deficiency of propionyl-CoA carboxylase. This enzyme is composed of two non-identical subunits, α and β, which are encoded by the PCCA and PCCB genes, respectively. An enzyme deficiency can result from mutations in either PCCA or PCCB. To elucidate the mutation spectrum in Japanese patients, we have performed a mutation analysis of 30 patients with PA, which included nine previously reported patients. The study revealed that 15 patients were α-subunit deficient and 15 patients were β-subunit deficient. Seven novel mutations were found (IVS18 − 6C > G, 1746G > A, C398R, G197E and IVS18 + 1G > A in the PCCA; A153P and IVS9 + 1G > T in the PCCB). Among these Japanese patients with α-subunit deficiencies, 923–924insT, IVS18 − 6C > G, and R399Q mutations were frequent and the total allelic frequency of these three mutations combined was 56% (17/30). This is in sharp contrast to the mutation spectrum found in Caucasian patients, where no prevalent mutations have been identified. Among the β-subunit deficiencies, there were three frequent mutations; R410W, T428I, and A153P, whose allelic frequencies were 30, 26.7, and 13.3%, respectively. In conclusion, a limited number of mutations are predominant in both PCCA and PCCB genes among Japanese patients with propionic acidemia.

We report two brothers with microcephaly, cerebellar atrophy, and focal segmental glomerulosclerosis. The elder brother showed nephrotic syndrome from 2 years of age and died of renal failure at 8 years of age. The younger brother showed mild proteinuria, from 2 years of age, and his renal function was still preserved at 15 years of age. We propose that our patients may be affected with a mild form of Galloway-Mowat syndrome or another autosomal recessive syndrome with focal segmental glomerulosclerosis and central nervous system abnormalities.

We report a 19-month-old boy with Menkes' syndrome that was complicated by a progressive sliding hiatal hernia. He presented with convulsions, developmental delay, elongation and tortuosity of major cerebral arteries, and diverticulae of the bladder at 4 months of age. Based on the diagnosis of Menkes' syndrome, treatment with intravenous or subcutaneous copper-histidine administration was initiated at 6 months of age. At 13 months of age, he vomited frequently owing to sliding hiatal hernia, which progressed rapidly and required surgical treatment. Connective tissue abnormalities are characteristic complications of Menkes' syndrome. Sliding hiatal hernia is probably one of the connective tissue manifestations and should be carefully evaluated in patients with Menkes' syndrome demonstrating recurrent gastrointestinal and/or respiratory symptoms. ( J Child Neurol 2002;17:401-402).

The doublecortin (DCX) gene was recently found to be involved in patients with X-linked lissencephaly and subcortical band heterotopia or double cortex syndrome. We have studied the coding regions of the DCX gene in 11 Japanese patients with cortical dysplasia and have identified three different mutations (R186C in exon 3, R272X and R303X in exon 5) in four sporadic female cases. R272X, which has been detected in two unrelated cases, is a novel mutation. Although the number of cases studied remains limited, exon 5 may be a common mutational site in Japanese patients in contrast to many previus reports concerning exons 2 and 3.

We identified three different point mutations in the glutaryl-CoA dehydrogenase (GCDH) gene in two unrelated Japanese patients with glutaric aciduria type I (GA-I). One patient was a homozygote for Arg355His and the other a compound heterozygote for Ser305Leu and Met339Val. Arg355His and Met339Val are mutations hitherto undescribed, and all three mutations are predicted to alter the secondary structure of GCDH. Molecular analysis is useful for definite diagnosis and/or prenatal diagnosis of GA-I. Am. J. Med. Genet. 80:327–329, 1998. © 1998 Wiley-Liss, Inc.

Smith-Magenis syndrome (SMS) is a contiguous syndrome caused by an interstitial deletion of chromosome 17p11.2. The clinical SMS spectrums include short stature, brachydactyly, developmental delay, dysmorphic features, mental retardation, hyperactivity, self-injury, seizures, and sleep abnormalities (especially, reduced REM sleep). Here we attempted to define the minimum common deletion at 17p11.2 in 8 Japanese patients with SMS using molecular cytogenetic approaches, including a prophase fluorescence in situ hybridization (FISH) ordering system and a stretched DNA fiber FISH. Our precise deletion mapping constructed by FISH revealed that one patient with SMS showed a much smaller deletion at 17p11.2 as compared with the other 7 patients with SMS. LLGL1 and FLII, previously mapped within the SMS critical deletion, were mutually nested, and retained on both chromosomes 17 in two patients. ZNF179, a RING finger protein family gene, on the SMS critical region was deleted on one of the two homologues 17p11.2 in 6 out of 8 patients with SMS in the present study. ZNF179 is a neuronal gene mapped on the SMS critical deletion and seems to be one of the candidates most likely to be affected with an impairment of the CNS in SMS patients. However, ZNF179 was retained on both 17p11.2 in two SMS patients exhibiting clinical findings characteristic of SMS, suggesting that ZNF179 might not be associated with the neurobehavioral impairments in SMS. Furthermore, DNA fragments from the region at 17p11.2 contained highly repetitive sequences, probably including the low-copy repeats (LCRs) associated with the deletion/duplication mechanism through non-allelic homologous recombination in the patients with SMS.