Clinical features and mutation of NPHP5 in two Chinese siblings with Senior‐Løken syndrome

Senior‐Løken syndrome is a rare syndromic form of nephronophthisis that is associated with retinal dystrophy. Presently, seven genes (NPHP1‐6 and NPHP10) have been associated with Senior‐Løken syndrome. NPHP5 mutations are known to cause classical Senior‐Løken syndrome. Here, we report two sisters (II‐4, II‐5) from a Chinese Han ethnic family who presented with classical Senior‐Løken syndrome. Both affected sisters exhibited Leber's congenital amaurosis and juvenile nephronophthisis that progressed to end‐stage renal disease by the age of 16 years and 9 months in patient II‐4 and 12 years and 9 months in patient II‐5. Sequence analysis showed a homozygous truncated mutation in NPHP5, c.1090C>T (p.R364X), in the patient II‐4. This mutation is predicted to introduce a new open reading frame that results in the truncation of the C‐terminal 235 amino acids of nephrocystin‐5 and its consequent loss of function. Both parents carried a single heterozygous mutation in the same position, and no homozygous deletion of NPHP1 was found in this pedigree.