A novel mutation in the complement factor B gene (CFB) and atypical hemolytic uremic syndrome.

We report the case of an 8-year-old girl diagnosed with atypical hemolytic uremic syndrome (aHUS) with a complement factor B (CFB) gene mutation. aHUS is a disease of complement dysregulation. In approximately 50% of patients, mutations are identified in genes encoding regulators of complement-complement factor H (CFH), membrane cofactor protein or complement factor I (CFI)-or activators of complement-complement factor B (CFB) or C3. The mutation in this patient was identified in exon 12 of CFB and changes a lysine at amino acid position 533 to an arginine (c.1598A>G p.Lys533Arg). The two other mutations previously reported in CFB associated with aHUS are c.858C>G, p.F286L in exon 6 and c.967A>Gp.K323E in exon 7.

Unique phenotype in a patient with CHARGE syndrome.

CHARGE is a phenotypically heterogeneous autosomal dominant disorder recognized as a cohesive syndrome since the identification of CHD7 as a genetic etiology. Classic features include: Coloboma, Heart defects, Atresia choanae, Retarded growth and development, Genitourinary abnormalities, and Ear anomalies and/or deafness. With greater accessibility to genetic analysis, a wider spectrum of features are emerging, and overlap with disorders such as DiGeorge syndrome, Kallmann syndrome, and Hypoparathyroidism Sensorineural Deafness and Renal Disease syndrome, is increasingly evident. We present a patient with a unique manifestation of CHARGE syndrome, including primary hypoparathyroidism and a limb anomaly; to our knowledge, he is also the first CHARGE subject reported with bilateral multicystic dysplastic kidneys. Furthermore, with structural modeling and murine expression studies, we characterize a putative CHD7 G744S missense mutation. Our report continues to expand the CHARGE phenotype and highlights that stringent fulfillment of conventional criteria should not strictly guide genetic analysis.