A Mutation Analysis of the Phenylalanine Hydroxylase (<i>PAH</i>) Gene in the Israeli Population

Bercovich, Dani; Elimelech, Arava; Yardeni, Tal; Korem, Sigal; Zlotogora, Joël; Gal, Nurit; Goldstein, Nurit; Vilensky, Bela; Segev, R.; Avraham, S.; Loewenthal, Ron; Schwartz, Gerard; Anikster, Yair

doi:10.1111/j.1469-1809.2007.00425.x

Cited by 25 publications

(17 citation statements)

References 8 publications

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“…This loss of enzymatic function is most likely caused by conformational changes due to the presence of three additional amino acids (Gly-Leu-Gln) between the normal sequences encoded by exon 10 and exon 11 (Dworniczak et al, 1991). This mutation has been identified as the most common mutation in Mediterranean populations such as Turkey (Dobrowolski et al, 2011), Italy (Daniele et al, N. Ajami et al 2007), Spain (Desviat et al, 1999), Egypt (Effat et al, 1999), and Israel (Bercovich et al, 2008). In previous studies that have been performed in Iran, IVS10-11G>A was also identified with the highest frequency (Bonyadi et al, 2010;Zare-Karizi et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

A preliminary mutation analysis of phenylketonuria in southwest Iran

Ajami¹,

Nezhad²,

Foroughmand³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Phenylketonuria (PKU) is a heterogeneous and autosomal recessive metabolic disorder that is mainly caused by mutations in the hepatic phenylalanine hydroxylase (PAH) gene. This study was designed to identify PAH mutations within exons 6, 7, and 10-12 in PKU patients from southwest Iran. Forty Iranian patients with clinical and biochemically confirmed PKU were enrolled. The exons were sequenced directly and 13 different mutations were identified including I224T, S231P, R176X, c.592_613del22, R243X, R252W, R261Q, Y356X, V388M, IVS10-11G>A, IVS11+1G>C, IVS11-2A>G, and Q375R, which were associated with 23 genotypes. A novel sequence variant, Q375R (c.1124A>G), was detected in exon 11. In one patient, a typical genotype with more than two mutations (R243X/S231P/ S231P) was found. Seven different polymorphisms and three new variants were also detected in intron regions of PAH. A high mutation spectrum was predicted in the southwestern region of Iran due to its ethnic heterogeneity, especially the Khuzestan Province. The detection PAH mutations in southwest Iran of 13 different mutations, corresponding to a mutation detection rate of 53.75%, confirmed this phenomenon.

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Section: Discussionmentioning

confidence: 99%

A preliminary mutation analysis of phenylketonuria in southwest Iran

Ajami¹,

Nezhad²,

Foroughmand³

et al. 2013

Genet. Mol. Res.

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“…Another genetic recessive disease prevalent among Jews of Yemenite extraction is Phenylketonuria. It is estimated to affect 1: 5,000 live births in Jews of Yemenite extraction [21] . All affected subjects have the same molecular defect, a deletion spanning the third exon of the phenylalanine hydroxylase gene [22] .…”

Section: Discussionmentioning

confidence: 99%

Familial Hyperkalemia and Hypertension (FHHt) and KLHL3: Description of a Family with a New Recessive Mutation (S553L) Compared to a Family with a Dominant Mutation, Q309R, with Analysis of Urinary Sodium Chloride Cotransporter

Bassat

Carmon²,

Hanukoglu³

et al. 2017

Nephron

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Background: Familial hyperkalemia and hypertension (FHHt) is an inherited disorder manifested by hyperkalemia and hypertension. The following four causative genes were identified: WNK1, WNK4, CUL3, and KLHL3. For the first 3 genes, inheritance is autosomal dominant. For KLHL3, inheritance is mostly dominant. A few cases with autosomal recessive disease were described. The mechanism of these 2 modes of inheritance is not clear. In the recessive form, the phenotype of heterozygotes is not well described. Methods: Clinical and genetic investigation of members of 2 families was performed, one with recessive FHHt, and the other, an expansion of a family with Q309R KLHL3 dominant mutation, previously reported by us. Urinary exosomal sodium chloride cotransporter (NCC) was measured. Results: A family with recessive FHHt caused by a new KLHL3 mutation, S553L, is described. This consanguineous Jewish family of Yemenite extraction, included 2 homozygous and 7 heterozygous affected subjects. Increased urinary NCC was found in the affected members of the family with dominant Q309R KLHL3 mutation. In the recessive S553L family, homozygotes appeared to have increased urinary NCC abundance. Surprisingly, heterozygotes seemed to have also increased urinary NCC, though at an apparently lower degree. This was not accompanied by a clinical phenotype. Conclusions: A new recessive mutation in KLHL3 (S553L) was identified in FHHt. Increased urinary NCC was found in affected members (heterozygous) with dominant KLHL3 Q309R, and in affected members (homozygous) of the recessive form. Unexpectedly, in the recessive disease, heterozygotes seemed to have increased urinary NCC as well, apparently not sufficient quantitatively to produce a clinical phenotype.

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“…Each monomer has three structural domains: an N-terminal regulatory domain (residues 1-142), a catalytic domain (residues 143-410), and a C-terminal tetramerization domain (residues 411-452). The studies have provided information on the active site and binding sites for its substrate and cofactor [2].…”

Section: Introductionmentioning

confidence: 99%