A Nonsense Mutation inFAM161AIs a Recurrent Founder Allele in Dutch and Belgian Individuals With Autosomal Recessive Retinitis Pigmentosa

Abstract

A founder mutation in FAM161A p.(Arg437*) underlies approximately 2% of arRP cases in the Dutch and Belgian populations. The age of onset of the retinal dystrophy appears variable, but progression can be steep, with almost complete loss of central vision later in life.

Unique combination of clinical features in a large cohort of 100 patients with retinitis pigmentosa caused by FAM161A mutations

“…All Jewish FAM161A patients are either homozygous or compound heterozygous for two founder mutations (c.1567C > T and c.1355_6del; Supplementary Table S2). Clinical findings in a small number of patients with FAM161A-RP have been reported previously, including by ourselves 10,[17][18][19][20]28 . In the present paper, we report on the largest set of FAM161A patients studied thus far worldwide.…”

“…The most frequent initial symptom was night blindness, followed by loss of visual fields and decrease in visual acuity. Most of the patients reported that the initial symptom of night blindness appeared in childhood (39 patients before the age of 10) or during adolescence (26 patients between the ages of [11][12][13][14][15][16][17][18][19][20], which represents 78% of the 83 patients for whom this data was available ( Supplementary Table S2).…”

“…Since the identification of FAM161A as a cause for ARRP in 2010, 13 pathogenic mutations have been reported ( Supplementary Fig. S1 and Supplementary Table S1) 9,10,[17][18][19][20][21][22][23][24][25][26][27] . Two of these mutations (frameshift c.1355_6del and nonsense c.1567C > T) were originally identified to be relatively common among the Jewish population in Israel 9 and two were reported in Palestinian families 9,20 .…”

“…Mutations in this gene are the most common cause of ARRP in Israel (18.2%, Fig. 1a) while the frequency elsewhere is relatively low (ranging from 0.003 to 2% 17,19,21,22,28 ).…”

“…To date, a total of 82 patients with ARRP caused by FAM161A mutations have been reported in various publications (42 residing in Israel and 53 worldwide), with a phenotype that largely falls within the spectrum described in other genes causing ARRP 9,10,[17][18][19][20][21][22]28 . In the current study we further explore the clinical phenotype in a large cohort of 100 Israeli patients harboring FAM161A mutations for whom clinical data was available.…”