A case report of NPHP1 deletion in Chinese twins with nephronophthisis

Abstract

Background: Nephronophthisis (NPHP) is a rare autosomal recessive inherited disorder with high heterogeneity. The majority of NPHP patients progress to end-stage renal disease (ESRD) within the first three decades of life. As an inherited disorder with highly genetic heterogeneity and clinical presentations, NPHP still poses a challenging task for nephrologists without special training to make a well-judged decision on its precise diagnosis, let alone its mechanism and optimal therapy. Case presentation: A Chinese family with NPHP was recruited in current study. The clinical characteristics (including findings from renal biopsy) of NPHP patients were collected from medical records and the potential responsible genes were explored by the whole exome sequencing (WES). A homozygous deletion of NPHP1 (1-20 exons) was found in both affected patients, which was further confirmed by quantitative PCR. Conclusions: Homozygous full gene deletion of the NPHP1 gene was identified in a Chinese family with NPHP, which was the molecular pathogenic basis of this disorder. Furthermore, identification of the pathogenic genes for those affected patients can help to have a full knowledge on NPHP's molecular mechanism and precise treatment.

Different Clinical Courses of Nephronophthisis in Dizygotic Twins

“…A previous case report from China of twins with a homozygous NPHP1 deletion demonstrated a similar progression of kidney dysfunction ( 8 ), although siblings with NPHP1 deletion often show different phenotypes and different clinical courses ( 9 , 10 ). The contributing factors to the phenotypic variance are yet to be elucidated.…”

NPHP1‐Related ciliopathies: A new case and major review of the ophthalmic manifestations of 147 reported cases

“…There were 646 NPHP cases, 23 Joubert Syndrome cases, and nine Senior Loken cases. 125 NPHP cases, 13 Joubert syndrome cases, and all nine Senior Loken cases had ophthalmic abnormalities with a total of 147 cases overall with eye manifestations 9‐56 . Most common eye manifestations include retinal abnormalities ( n = 70) including retinitis pigmentosa and retinal dystrophies as well as nystagmus ( n = 19) and strabismus ( n = 14).…”

“…125 NPHP cases, 13 Joubert syndrome cases, and all nine Senior Loken cases had ophthalmic abnormalities with a total of 147 cases overall with eye manifestations. 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 Most common eye manifestations include retinal abnormalities ( n = 70) including retinitis pigmentosa and retinal dystrophies as well as nystagmus ( n = 19) and strabismus ( n = 14). Less commonly reported eye manifestations included palpebral fissure abnormalities ( n = 5), cataracts ( n = 3), epicanthal folds ( n = 2), telecanthus ( n = 1), and exophthalmos ( n = 1).…”