Jos Jansen

36 Chapter 2 Table 1 Overview of the genetic and clinical features of the CCDC115-deficient families Family IV (y.o.b.) Zygosity Allele frequen- cy (ExAc browser) gDNA change (chr2(GRCh37)) cDNA change Protein change CDG Elevated choles- terol and LDL-C Ele- vated ALP Elevated AT Cerulo plasmin Hepatic pheno- type Neurologi- cal pheno- type N O 1 1.1 (‘00) 1.2 (‘04) 1.3 (‘12) Homozy- gous 8.253e-06 g.131099607A > G c.[92T > C]; [92T > C] p.[Le- u31Ser]; [Le- u31Ser] + + + ++ + low cirrhosis, hepato- megaly Hypotonia, PMD 2 2.1 (’08) Homozy- gous 8.253e-06 g.131099607A > G c.[92T > C]; [92T > C] p.[Le- u31Ser]; [Le- u31Ser] + + + ++ + low hepato- megaly, dry cop- per 125 µg/g PMD 3 3.1 (’89) Homozy- gous 8.253e-06 g.131099607A > G c.[92T > C]; [92T > C] p.[Le- u31Ser]; [Le- u31Ser] + - + ++ + low fibrosis, steatosis, necrotic lesions Hypotonia, PMD, sei- zures 4 1 4.1 (’02) 4.2 (’03) Homozy- gous 0 g.131099668C > A c.[31G > T]; [31G > T] p.[Asp- 11Tyr]; [Asp- 11Tyr] + - + ++ + n.d. liver failure 2 - 5 3 5.1 (’14) Com- pound Hetero- zygous 8.253e-06 / NA g.131099607A > G / g.(130939272_131096872)_ (131116671_?)del c.[92T > C]; [(?_-258)_ (*1245_?) del] p.[Le- u31Ser]; [p.0?] + + + ++ ++ n.d. liver failure hypotonia Abbreviations are as follows: y.o.b., year of birth; CDG, Congenital Disorders of Glycosylation; N, N-glycosylation measured by isoelectric focusing of serum transferrin; O, O-glycosylation measured by isoelectric focusing of serum apoCIII; LDL-C, low-density lipoprotein; AT, serum aminotransferases; ALP, serum alkaline phosphatase; PMD, psychomotor disability; n.d., not determined. 1 Sibling 4.1 died at the age of 9 years due to liver failure after repeated liver transplantation. 2 Both siblings needed liver transplantation 3 Individual 5.1 died of liver failure at the age of 7 months