PURPOSE: Designating mutations as recessive or dominant is a function of the effect of the mutant allele on the phenotype. Genes in which both classes of mutations are known to exist are particularly interesting to study because these mutations typically define distinct pathogenic mechanisms at the molecular level. METHODS: We studied two consanguineous families with different eye phenotypes and used a combination of candidate gene analysis and homozygosity mapping to identify the underlying genetic defects. RESULTS: In one family, a novel BFSP2 mutation causes autosomal recessive diffuse cortical cataract with scattered lens opacities, and in another, a novel PITX3 mutation causes an autosomal recessive severe form of anterior segment dysgenesis and microphthalmia. CONCLUSION: We show that BFSP2 and PITX3, hitherto known to cause eye defects only in a dominant fashion, can also present recessively. The likely null nature of both mutations and lack of manifestation in heterozygotes strongly argues for a mechanism other than loss of function in the previously reported dominant mutations in these two genes. Thus, study of consanguineous populations has the additional advantage of not only identifying novel recessive genes but also defining the mutational mechanism of dominant disorders.
PURPOSE: Designating mutations as recessive or dominant is a function of the effect of the mutant allele on the phenotype. Genes in which both classes of mutations are known to exist are particularly interesting to study because these mutations typically define distinct pathogenic mechanisms at the molecular level. METHODS: We studied two consanguineous families with different eye phenotypes and used a combination of candidate gene analysis and homozygosity mapping to identify the underlying genetic defects. RESULTS: In one family, a novel BFSP2 mutation causes autosomal recessive diffuse cortical cataract with scattered lens opacities, and in another, a novel PITX3 mutation causes an autosomal recessive severe form of anterior segment dysgenesis and microphthalmia. CONCLUSION: We show that BFSP2 and PITX3, hitherto known to cause eye defects only in a dominant fashion, can also present recessively. The likely null nature of both mutations and lack of manifestation in heterozygotes strongly argues for a mechanism other than loss of function in the previously reported dominant mutations in these two genes. Thus, study of consanguineous populations has the additional advantage of not only identifying novel recessive genes but also defining the mutational mechanism of dominant disorders.
Authors: Fatema Zahrani; Mohammed A Aldahmesh; Muneera J Alshammari; Selwa A F Al-Hazzaa; Fowzan S Alkuraya Journal: Am J Hum Genet Date: 2013-02-28 Impact factor: 11.025
Authors: Shams Anazi; Sateesh Maddirevula; Vincenzo Salpietro; Yasmine T Asi; Saud Alsahli; Amal Alhashem; Hanan E Shamseldin; Fatema AlZahrani; Nisha Patel; Niema Ibrahim; Firdous M Abdulwahab; Mais Hashem; Nadia Alhashmi; Fathiya Al Murshedi; Adila Al Kindy; Ahmad Alshaer; Ahmed Rumayyan; Saeed Al Tala; Wesam Kurdi; Abdulaziz Alsaman; Ali Alasmari; Selina Banu; Tipu Sultan; Mohammed M Saleh; Hisham Alkuraya; Mustafa A Salih; Hesham Aldhalaan; Tawfeg Ben-Omran; Fatima Al Musafri; Rehab Ali; Jehan Suleiman; Brahim Tabarki; Ayman W El-Hattab; Caleb Bupp; Majid Alfadhel; Nada Al Tassan; Dorota Monies; Stefan T Arold; Mohamed Abouelhoda; Tammaryn Lashley; Henry Houlden; Eissa Faqeih; Fowzan S Alkuraya Journal: Hum Genet Date: 2017-09-22 Impact factor: 4.132
Authors: Nisha Patel; Deepti Anand; Dorota Monies; Sateesh Maddirevula; Arif O Khan; Talal Algoufi; Mohammed Alowain; Eissa Faqeih; Muneera Alshammari; Ahmed Qudair; Hadeel Alsharif; Fatimah Aljubran; Hessa S Alsaif; Niema Ibrahim; Firdous M Abdulwahab; Mais Hashem; Haifa Alsedairy; Mohammed A Aldahmesh; Salil A Lachke; Fowzan S Alkuraya Journal: Hum Genet Date: 2016-11-22 Impact factor: 4.132