Novel mutations in two Saudi patients with congenital retinal dystrophy

Abstract

To report novel mutations in two Saudi children with clinical features of Leber congenital amaurosis (LCA) and Alström syndrome. Case reports. Case 1 was a child with phenotypic features of LCA including oculodigital sign, bilateral enophthalmos, nystagmus, pale disc, and retinal changes. Direct sequencing of the coding sequence of GUCY2D revealed a missense mutation affecting highly conserved position (c. 743C > T; p.S248 L). Case 2 describes a girl with marked nystagmus, photophobia, and retinal changes in both eyes with short and stubby fingers tapering at the distal phalanges. The electroretinograms were nonrecordable in each eye. She had a hearing aid in the left ear, mid-facial hypoplasia, bilateral enophthalmos, and insulin dependent diabetes. Mutation screening of candidates genes revealed a pathogenic mutation in ALMS1 gene (c. 8441C > A, p.S2814*). Two novel mutations causing phenotypic LCA and Alström syndrome in Saudi patients from consanguineous families expand the genotypic spectrum of congenital retinal dystrophies

Whole exome sequencing identifies rare biallelic ALMS1 missense and stop gain mutations in familial Alström syndrome patients

“…However, as of now, only a few studies on AS patients are published from Arab world (Chakroun et al, 2016). From Saudi Arabia, only three published studies are listed in PUBMED (Aldahmesh et al, 2009, Safieh et al, 2016, Bakar et al, 2017). Bakar AA et al, (Bakar et al, 2017) has described a homozygous frameshift mutation leading to a premature termination codon (p. Arg4052Glyfs ∗ 2) in ALMS1 gene in an AS patient presenting clinical manifestations like diabetic ketoacidosis, hearing loss and blindness.…”

“…Bakar AA et al, (Bakar et al, 2017) has described a homozygous frameshift mutation leading to a premature termination codon (p. Arg4052Glyfs ∗ 2) in ALMS1 gene in an AS patient presenting clinical manifestations like diabetic ketoacidosis, hearing loss and blindness. Safieh et al (2016) reported two novel mutations including a missense mutation (p.S248L) and protein truncation mutation (p.S2814 *) in AS patients from 2 different families with a history of consanguinity and congenital retinal dystrophies. Aldahmesh et al (2009) identified four novel homozygous pathogenic mutations in 4 sporadic AS cases.…”

“…Especially, studying Bedouin communities of Saudi Arabia, where consanguinity is a normal cultural norm (Abedalthagafi, 2019), may present a great opportunity to identify novel mutations in known AS causative gene. So far, only few investigators have studied the molecular basis of AS syndrome in Saudi Arabia, that too in sporadic cases (Aldahmesh et al, 2009, Safieh et al, 2016, Bakar et al, 2017). In the current study, whole exome sequencing of multiple AS patients belonging to 2 different Bedouin families was performed for identifying the genetic basis of the familial forms of disease.…”

Alström syndrome

“…Regarding reports from Saudi Arabia, to date, 2 report cases by Aldahmesh et al and Abu-Safieh et al have reveled 4 and 2 novel mutations respectively. [ 7 , 8 ]…”

Identification of a Rare Exon 19 Skipping Mutation in ALMS1 Gene in Alström Syndrome Patients From Two Unrelated Saudi Families

“…By using whole-exome sequencing, earlier our group found causative rare biallelic mutations in the ALMS1 gene in exon 8 (T376S in exon 5, and S909 * ) and exon 10 (R2721 * ) among AS patients from two other unrelated Saudi families ( 28 ). These truncating mutations at residues S909 and R2721 possibly create an unstable protein due to loss of CC domain and ALMS motif on the C-terminal end which led to intracellular truncated protein degradation ( 31 ). Another retrospective study from Saudi Arabia has reported the identification of 10 ALMS1 different mutations (E3649 * , Q2648 * , p.E913Sfs * 20, p.Ser2102 * , p.Arg2928 * , p.Ser2102 * , p.Arg2722 * , p.P3911QfsX16, p.Ser908 * , IVS18-3A>T) in 19 Alström cases presenting different ophthalmic phenotypes from 13 Saudi families.…”