Mutational spectrum of the<i>TYR</i>and<i>SLC45A2</i>genes in Pakistani families with oculocutaneous albinism, and potential founder effect of missense substitution (p.Arg77Gln) of tyrosinase

Shah, Sajjad Ali; Raheem, Nafeesa; Daud, Shakeela; Mubeen, J.; Shaikh, Adnan Al; Baloch, Abdul Hameed; Nadeem, Asif; Tayyab, Muhammad; Babar, Masroor Ellahi; Ahmad, Jamil

doi:10.1111/ced.12612

Cited by 13 publications

(14 citation statements)

References 22 publications

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“…In this study we investigated the founder effects of these three mutations in unrelated OCA families in Iran. The potential founder effect of p.R77Q which was the most common TYR mutation in the Pakistani population was also reported by Shah et al (16).…”

Section: Discussionsupporting

confidence: 64%

“…Knowledge about mutation distribution diversity may be helpful for early and more cost effective mutation screening and genetic counseling (15,16).…”

Section: Discussionmentioning

confidence: 99%

“…The founder effect is a feature of populations with a high degree of intermarriage or geographic isolation (16). The overall rate of consanguineous marriage in Iran is about 38.6% and this can increase the probability of incidence of genetic disorders due to common ancestors (17,18).…”

Section: Discussionmentioning

confidence: 99%

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Potential Founder Effect of Tyrosinase Gene Mutations in Oculocutaneous Albinism Families from West of Iran

Deilamani

Akbari

2017

J Human Gen Genom

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Background: Non syndromic oculocutaneous albinism type (OCA) is caused by mutations in tyrosinase (TYR), OCA2, TYRP1, MATP (SLC45A2), SLC24A5 and C10ORF11 genes. Screening for mutations is important in families with oculocutaneous albinism patients in order to accurately diagnose the albinism type, genetic counseling and future therapeutic purposes. Objectives: The Aim of this study was to investigate the founder effect of most frequent mutations in OCA patients. Methods: TYR gene was sequenced in 26 unrelated inbred OCA families as well as 56 unrelated healthy individuals. In addition, homozygosity mapping was performed using 13 STR markers for 6 OCA loci (TYR, OCA2, TYRP1, MATP (SLC45A2), SLC24A5 and C10ORF11 genes). Different mutations were found in these genes from which a single base duplication (c.286dupA) and two single base substitutions c.996G > A (p.M332I) and c.230G > A (p.R77Q) had the most frequencies among the OCA families. In order to investigate the founder effect of these mutations, the haplotypes of two STR markers (TYR-S1 and TYR-S2) inside the TYR gene were ascertained. Results: It was revealed that families with similar mutation harbored similar haplotype for the TYR STR markers too. Conclusions: We conclude that these mutations are possible founder mutations in the Iranian population.

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Section: Discussionsupporting

confidence: 64%

“…Knowledge about mutation distribution diversity may be helpful for early and more cost effective mutation screening and genetic counseling (15,16).…”

Section: Discussionmentioning

confidence: 99%

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Potential Founder Effect of Tyrosinase Gene Mutations in Oculocutaneous Albinism Families from West of Iran

Deilamani

Akbari

2017

J Human Gen Genom

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“…In family 11, proband (III-2) was noted to have a novel pathogenic vari- 18 It has also been reported as cause of oculocutaneous albinism type 1 in a family with three affected siblings. 19 Therefore, this variant is the probably cause of hypopigmentation noted in him.…”

Section: Resultsmentioning

confidence: 92%

Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome

et al. 2018

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Waardenburg syndrome (WS) is a disorder of neural crest cell migration characterized by auditory and pigmentary abnormalities. We investigated a cohort of 14 families (16 subjects) either by targeted sequencing or whole-exome sequencing. Thirteen of these families were clinically diagnosed with WS and one family with isolated non-syndromic hearing loss (NSHL). Intrafamilial phenotypic variability and non-penetrance were observed in families diagnosed with WS1, WS2 and WS4 with pathogenic variants in PAX3, MITF and EDNRB, respectively. We observed gonosomal mosaicism for a variant in PAX3 in an asymptomatic father of two affected siblings. For the first time, we report a biallelic pathogenic variant in MITF in a subject with WS2 and a biallelic variant in EDNRB was noted in a subject with WS2. An individual with isolated NSHL carried a pathogenic variant in MITF. Blended phenotype of NSHL and albinism was observed in a subject clinically diagnosed to have WS2. A phenocopy of WS1 was observed in a subject with a reported pathogenic variant in GJB2, known to cause isolated NSHL. These novel and infrequently reported observations exemplify the allelic and genetic heterogeneity and show phenotypic diversity of WS.

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“…Nonsyndromic OCA includes four types, i.e., OCA1 (MIM#203100), OCA2 (MIM#203200), OCA3 (MIM#203290), and OCA4 (MIM#606574), caused by mutations in the tyrosinase gene ( TYR ), OCA2 , tyrosinase-related protein gene ( TYRP1 ), and solute carrier family 45 member 2 gene ( SLC45A2 ), respectively [4–6]. OCA1 and OCA2 are the two most frequent types of OCA, accounting for approximately 50% and 30% of cases, respectively [5, 7]. OCA1 could be further subgrouped into OCA1A and OCA1B.…”

Section: Introductionmentioning

confidence: 99%

Mutation analysis of a Chinese family with oculocutaneous albinism

et al. 2016

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Oculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by either complete lack of or a reduction in melanin biosynthesis in the skin, hair, and eyes. OCA1, the most common and severe type, is caused by mutations in the tyrosinase (TYR) gene. In this study, we report a Chinese family with two members affected by OCA. Blood samples were collected from all family members. Genomic DNA was isolated from blood leukocytes, and all coding exons and adjacent intronic sequences of the TYR gene were examined for mutation analysis using polymerase chain reaction (PCR)-based sequencing. A pedigree chart was drawn, and clinical examinations and paraclinical tests were performed. Compound heterozygous mutations in TYR (c.832C>T and c.929_930insC, which resulted in p.Arg278* and p.Arg311Lysfs*7, respectively) were identified in the two patients with milky skin, white hair, photophobia, and reduced visual acuity, while other family members only carried one of two heterozygous mutations. In addition, a homozygous missense mutation c.814G>A (p.Glu272Lys) in the solute carrier family 45 member 2 (SLC45A2) gene was found in both patients and unaffected family members, suggesting that this may not be a causative mutation. The findings of this study expand the mutational spectrum of OCA. Compound heterozygous mutations (c.832C>T and c.929_930insC) in the TYR gene may be responsible for partial clinical manifestations of OCA, while the homozygous missense mutation c.814G>A (p.Glu272Lys) in the SLC45A2 gene may not be associated with OCA.

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Mutational spectrum of theTYRandSLC45A2genes in Pakistani families with oculocutaneous albinism, and potential founder effect of missense substitution (p.Arg77Gln) of tyrosinase

Cited by 13 publications

References 22 publications

Potential Founder Effect of Tyrosinase Gene Mutations in Oculocutaneous Albinism Families from West of Iran

Potential Founder Effect of Tyrosinase Gene Mutations in Oculocutaneous Albinism Families from West of Iran

Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome

Mutation analysis of a Chinese family with oculocutaneous albinism

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