Scientific background:

Summary: Homozygous or compound heterozygous mutations of NPHP1 cause nephronophthisis 1, Senior-Loken syndrome 1, or Joubert syndrome 4.

Gene: The NPHP1 gene, which is located on chromosome 2 (2q13) spans about 85kb. Two spice variants exists with 20 and 4 exons. In the shorter splice variant, exon 4 is 376 bases longer.

Pathology: Nearly 80% of patients with nephronophthisis 1 show a homozygous deletion of about 290 kb. But splice and missense mutations have also been reported.

Test strategy: As in many patients a homozygous deletion of a large part of the gene is the cause of disease, in most cases the diagnosis can be proved by demonstrating amplification failure during the first step of sequencing analysis.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		30 working days
		Effort		medium
		Specimen		DNA
		Quality assessment		Internal quality control only
	All known and new missense, nonsense and splice mutations can be detected.
	clinical test	Method		Carrier testing
		Turn-around time		5 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	The test is only specific about the mutation already known in this kindred.

Literature: 

Hildebrandt F et al. (1997) A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1.
Hildebrandt F et al. (1997) A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1.
Saunier S et al. (2000) Characterization of the NPHP1 locus: mutational mechanism involved in deletions in familial juvenile nephronophthisis.