Fowzan S Alkuraya


Affiliation: King Faisal Specialist Hospital and Research Centre
Country: Saudi Arabia


  1. Shaheen R, Schmidts M, Faqeih E, Hashem A, Lausch E, Holder I, et al. A founder CEP120 mutation in Jeune asphyxiating thoracic dystrophy expands the role of centriolar proteins in skeletal ciliopathies. Hum Mol Genet. 2015;24:1410-9 pubmed publisher
    ..These results are consistent with aberrant CEP120 being implicated in the pathogenesis of JATD and expand the role of centriolar proteins in skeletal ciliopathies. ..
  2. Aldahmesh M, Li Y, Alhashem A, Anazi S, Alkuraya H, Hashem M, et al. IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet-Biedl syndrome. Hum Mol Genet. 2014;23:3307-15 pubmed publisher
    ..This is the first time an intraflagellar transport (IFT) gene is implicated in the pathogenesis of BBS, highlighting the genetic complexity of this disease. ..
  3. Shaheen R, Tasak M, Maddirevula S, Abdel Salam G, Sayed I, Alazami A, et al. PUS7 mutations impair pseudouridylation in humans and cause intellectual disability and microcephaly. Hum Genet. 2019;138:231-239 pubmed publisher
    ..cerevisiae pus7Δ trm8Δ mutants. Our results confirm that PUS7 is a bona fide Mendelian disease gene and expand the list of human diseases caused by impaired pseudouridylation. ..
  4. Shaheen R, Jiang N, Alzahrani F, Ewida N, Al Sheddi T, Alobeid E, et al. Bi-allelic Mutations in FAM149B1 Cause Abnormal Primary Cilium and a Range of Ciliopathy Phenotypes in Humans. Am J Hum Genet. 2019;104:731-737 pubmed publisher
    ..We conclude that FAM149B1 is required for normal ciliary biology and that its deficiency results in a range of ciliopathy phenotypes in humans along the spectrum of Joubert syndrome. ..
  5. Shamseldin H, Makhseed N, Ibrahim N, Al Sheddi T, Alobeid E, Abdulwahab F, et al. NUP214 deficiency causes severe encephalopathy and microcephaly in humans. Hum Genet. 2019;138:221-229 pubmed publisher
    ..In addition, the typical rim staining of NUP214 is largely displaced, further supporting the deleterious effect of the variant. Our data expand the list of NUP genes that are mutated in encephalopathy disorders in humans. ..
  6. Maddirevula S, Alsahli S, Alhabeeb L, Patel N, Alzahrani F, Shamseldin H, et al. Expanding the phenome and variome of skeletal dysplasia. Genet Med. 2018;20:1609-1616 pubmed publisher
    ..16E-04), which is much higher than the global average. By expanding the phenotypic, allelic, and locus heterogeneity of skeletal dysplasia in humans, we hope our study will improve the diagnostic rate of patients with these conditions. ..
  7. Al Qattan M, Maddirevula S, Alkuraya F. A de novo TBX3 mutation presenting as dorsalization of the little fingers: A forme fruste phenotype of ulnar-mammary syndrome. Eur J Med Genet. 2019;: pubmed publisher
    ..We review the literature to confirm that this should be considered as a forme fruste phenotype of UMS. ..
  8. Stephen J, Maddirevula S, Nampoothiri S, Burke J, Herzog M, Shukla A, et al. Bi-allelic TMEM94 Truncating Variants Are Associated with Neurodevelopmental Delay, Congenital Heart Defects, and Distinct Facial Dysmorphism. Am J Hum Genet. 2018;103:948-967 pubmed publisher
    ..Our study suggests the genetic etiology of a recognizable dysmorphic syndrome with NDD and CHD and highlights the role of TMEM94 in early development. ..
  9. Alazami A, Maddirevula S, Seidahmed M, Albhlal L, Alkuraya F. A novel ISLR2-linked autosomal recessive syndrome of congenital hydrocephalus, arthrogryposis and abdominal distension. Hum Genet. 2019;138:105-107 pubmed publisher
    ..We suggest this syndrome may represent the human "knockout" phenotype for ISLR2. ..

More Information


  1. Shaheen R, Maddirevula S, Ewida N, Alsahli S, Abdel Salam G, Zaki M, et al. Genomic and phenotypic delineation of congenital microcephaly. Genet Med. 2019;21:545-552 pubmed publisher
    ..Our study refines the phenotype of CM, expands its genetics heterogeneity, and informs the workup of children born with this developmental brain defect. ..
  2. Maddirevula S, Alhebbi H, Alqahtani A, Algoufi T, Alsaif H, Ibrahim N, et al. Identification of novel loci for pediatric cholestatic liver disease defined by KIF12, PPM1F, USP53, LSR, and WDR83OS pathogenic variants. Genet Med. 2018;: pubmed publisher
    ..Our results expand the genetic heterogeneity of pediatric cholestatic liver disease and highlight the vulnerability of bile homeostasis to a wide range of molecular perturbations. ..
  3. Maddirevula S, Alzahrani F, Al Owain M, Al Muhaizea M, Kayyali H, Alhashem A, et al. Autozygome and high throughput confirmation of disease genes candidacy. Genet Med. 2019;21:736-742 pubmed publisher
    ..Our results should facilitate the timely relabeling of these candidate disease genes in relevant databases to improve the yield of clinical genomic sequencing. ..
  4. Derar N, Al Hassnan Z, Al Owain M, Monies D, Abouelhoda M, Meyer B, et al. De novo truncating variants in WHSC1 recapitulate the Wolf-Hirschhorn (4p16.3 microdeletion) syndrome phenotype. Genet Med. 2019;21:185-188 pubmed publisher
    ..Given the severe nature of the reported variants, the full phenotypic expression of WHSC1 may be further expanded by future reports of milder variants. ..
  5. Alkuraya F. Human knockout research: new horizons and opportunities. Trends Genet. 2015;31:108-15 pubmed publisher
    ..As I discuss in this review, the potentially wide implications of human knockout research warrant increased investment and multidisciplinary collaborations to overcome existing challenges and reap its benefits. ..
  6. Alsaif H, Khan A, Patel N, Alkuraya H, Hashem M, Abdulwahab F, et al. Congenital glaucoma and CYP1B1: an old story revisited. Hum Genet. 2018;: pubmed publisher
    ..We also encountered candidate causal variants in genes not previously linked to human diseases: BCO2, TULP2, and DGKQ. Our results both expand and refine the genetic spectrum of congenital glaucoma with important clinical implications. ..
  7. Abouelhoda M, Faquih T, El Kalioby M, Alkuraya F. Revisiting the morbid genome of Mendelian disorders. Genome Biol. 2016;17:235 pubmed
    ..Our study shows the importance of revisiting disease-related databases using public resources as well as of population-specific resources to improve the specificity of the morbid genome of Mendelian diseases in humans. ..
  8. Patel N, Anand D, Monies D, Maddirevula S, Khan A, Algoufi T, et al. Novel phenotypes and loci identified through clinical genomics approaches to pediatric cataract. Hum Genet. 2017;136:205-225 pubmed publisher
    ..Our study expands the phenotypic, allelic and locus heterogeneity of pediatric cataract. The high diagnostic yield of clinical genomics supports the adoption of this approach in this patient group. ..
  9. Anazi S, Maddirevula S, Salpietro V, Asi Y, Alsahli S, Alhashem A, et al. Correction to: Expanding the genetic heterogeneity of intellectual disability. Hum Genet. 2018;137:105-109 pubmed publisher
    ..Variant nomenclature discrepancy was identified in the article. ..
  10. Alkuraya F. Discovery of mutations for Mendelian disorders. Hum Genet. 2016;135:615-23 pubmed publisher
    ..Also discussed are some of the challenges that will gain more prominence as we approach the last phase of the effort to map all Mendelian genes. ..
  11. Shtir C, Aldahmesh M, Al Dahmash S, Abboud E, Alkuraya H, Abouammoh M, et al. Exome-based case-control association study using extreme phenotype design reveals novel candidates with protective effect in diabetic retinopathy. Hum Genet. 2016;135:193-200 pubmed publisher
    ..Extreme phenotype design when implemented in sequencing-based genome-wide case-control studies has the potential to reveal novel candidates with a smaller cohort size compared to standard study designs. ..
  12. Ghazi N, Abboud E, Nowilaty S, Alkuraya H, Alhommadi A, Cai H, et al. Treatment of retinitis pigmentosa due to MERTK mutations by ocular subretinal injection of adeno-associated virus gene vector: results of a phase I trial. Hum Genet. 2016;135:327-43 pubmed publisher
    ..Gene therapy for MERTK-related RP using careful subretinal injection of rAAV2-VMD2-hMERTK is not associated with major side effects and may result in clinical improvement in a subset of patients. ..
  13. Alazami A, Al Qattan S, Faqeih E, Alhashem A, Alshammari M, Alzahrani F, et al. Expanding the clinical and genetic heterogeneity of hereditary disorders of connective tissue. Hum Genet. 2016;135:525-540 pubmed publisher
    ..Our study expands the clinical spectrum of hereditary disorders of connective tissue and adds three novel candidate genes including two that are associated with a highly distinct syndrome. ..
  14. Siraj A, Masoodi T, Bu R, Beg S, Al Sobhi S, Al Dayel F, et al. Genomic Profiling of Thyroid Cancer Reveals a Role for Thyroglobulin in Metastasis. Am J Hum Genet. 2016;98:1170-1180 pubmed publisher
    ..001), including events of apparent clonal expansion. Our results suggest a previously unknown role of TG somatic mutations in the pathogenesis of PTC and its malignant evolution. ..
  15. Shamseldin H, Aldeeri A, Babay Z, Alsultan A, Hashem M, Alkuraya F. A lethal phenotype associated with tissue plasminogen deficiency in humans. Hum Genet. 2016;135:1209-11 pubmed publisher
    ..This is the first reported human knockout mutation of PLAT. The apparent association with hydranencephaly, diaphragmatic hernia and postnatal lethality requires further validation. ..
  16. Shaheen R, Hashem A, Abdel Salam G, Al Fadhli F, Ewida N, Alkuraya F. Mutations in CIT, encoding citron rho-interacting serine/threonine kinase, cause severe primary microcephaly in humans. Hum Genet. 2016;135:1191-7 pubmed publisher
  17. Alkuraya F. The application of next-generation sequencing in the autozygosity mapping of human recessive diseases. Hum Genet. 2013;132:1197-211 pubmed publisher
    ..This review will discuss the power of combining the best of both techniques in the mapping of recessive disease genes and offer some tips to troubleshoot potential limitations. ..
  18. Holohan B, Kim W, Lai T, Hoshiyama H, Zhang N, Alazami A, et al. Impaired telomere maintenance in Alazami syndrome patients with LARP7 deficiency. BMC Genomics. 2016;17:749 pubmed
    ..Together, these experiments demonstrate that in addition to the readily apparent developmental disorder associated with LARP7 deficiency, an underlying telomeropathy exists even in unaffected siblings of these individuals. ..
  19. Anazi S, Maddirevula S, Salpietro V, Asi Y, Alsahli S, Alhashem A, et al. Expanding the genetic heterogeneity of intellectual disability. Hum Genet. 2017;136:1419-1429 pubmed publisher
    ..Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms. ..
  20. Patel N, Khan A, Al Saif M, Moghrabi W, AlMaarik B, Ibrahim N, et al. A novel mechanism for variable phenotypic expressivity in Mendelian diseases uncovered by an AU-rich element (ARE)-creating mutation. Genome Biol. 2017;18:144 pubmed publisher
    ..This novel mutational mechanism for a Mendelian disease expands the potential mechanisms that underlie variable phenotypic expressivity in humans to also include 3' UTR mutations with tissue-specific pathology. ..
  21. Maddirevula S, Coskun S, Alhassan S, Elnour A, Alsaif H, Ibrahim N, et al. Female Infertility Caused by Mutations in the Oocyte-Specific Translational Repressor PATL2. Am J Hum Genet. 2017;101:603-608 pubmed publisher
    ..Data gathered from the families in this study suggest that the role of PATL2 is conserved in humans and expand our knowledge of the factors that are necessary for female meiosis. ..
  22. Siraj A, Masoodi T, Bu R, Parvathareddy S, Al Badawi I, Al Sanea N, et al. Expanding the spectrum of germline variants in cancer. Hum Genet. 2017;136:1431-1444 pubmed publisher
    ..Family history was lacking in 63.5% mutation-positive cases, shows that hereditary cancer need not appear familial and suggests that relaxed selection of cancer patients for hereditary cancer panels should be considered. ..
  23. Shamseldin H, Khalifa O, Binamer Y, Almutawa A, Arold S, Zaidan H, et al. KDF1, encoding keratinocyte differentiation factor 1, is mutated in a multigenerational family with ectodermal dysplasia. Hum Genet. 2017;136:99-105 pubmed publisher
    ..The recapitulation of the phenotype we observe in this family by the Kdf1-/- mouse suggests a causal role played by the KDF1 variant. ..
  24. Shamseldin H, Masuho I, Alenizi A, Alyamani S, Patil D, Ibrahim N, et al. GNB5 mutation causes a novel neuropsychiatric disorder featuring attention deficit hyperactivity disorder, severely impaired language development and normal cognition. Genome Biol. 2016;17:195 pubmed
  25. Shaheen R, Almoisheer A, Faqeih E, Babay Z, Monies D, Tassan N, et al. Identification of a novel MKS locus defined by TMEM107 mutation. Hum Mol Genet. 2015;24:5211-8 pubmed publisher
    ..This study shows that known MKS loci account for the overwhelming majority of MKS cases but additional loci exist including MKS13 caused by TMEM107 mutation. ..
  26. Shamseldin H, Alazami A, Manning M, Hashem A, Caluseiu O, Tabarki B, et al. RTTN Mutations Cause Primary Microcephaly and Primordial Dwarfism in Humans. Am J Hum Genet. 2015;97:862-8 pubmed publisher
    ..Our results expand the phenotype of RTTN-related disorders, hitherto limited to polymicrogyria, to include microcephalic primordial dwarfism with a complex brain phenotype involving simplified gyration. ..
  27. Manzini M, Xiong L, Shaheen R, Tambunan D, Di Costanzo S, Mitisalis V, et al. CC2D1A regulates human intellectual and social function as well as NF-?B signaling homeostasis. Cell Rep. 2014;8:647-55 pubmed publisher
    ..Homeostatic regulation of neuronal signaling pathways provides a mechanism whereby common founder mutations could manifest diverse symptoms in different patients. ..
  28. Shaheen R, Rahbeeni Z, Alhashem A, Faqeih E, Zhao Q, Xiong Y, et al. Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH. Am J Hum Genet. 2014;94:898-904 pubmed publisher
    ..This study shows that NLS represents the extreme end of a known inborn error of serine metabolism and highlights the power of genomic sequencing in revealing the unsuspected allelic nature of apparently distinct clinical entities. ..
  29. Patel N, Khan A, Mansour A, Mohamed J, Al Assiri A, Haddad R, et al. Mutations in ASPH cause facial dysmorphism, lens dislocation, anterior-segment abnormalities, and spontaneous filtering blebs, or Traboulsi syndrome. Am J Hum Genet. 2014;94:755-9 pubmed publisher
    ..These data support a genetic basis for a syndromic form of ectopia lentis and the role of aspartyl hydroxylation in human development. ..
  30. Faden M, Alzahrani F, Mendoza Londono R, Dupuis L, Hartley T, Kannu P, et al. Identification of a Recognizable Progressive Skeletal Dysplasia Caused by RSPRY1 Mutations. Am J Hum Genet. 2015;97:608-15 pubmed publisher
    ..This study highlights the role of gene-centric matchmaking tools to establish causal links to genes, especially for rare or previously undescribed clinical entities. ..
  31. Shaheen R, Abdel Salam G, Guy M, Alomar R, Abdel Hamid M, Afifi H, et al. Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism. Genome Biol. 2015;16:210 pubmed publisher
    ..Our study expands the number of biological pathways underlying primordial dwarfism and adds to a growing list of human diseases linked to abnormal tRNA modification. ..
  32. al Yacoub N, Shaheen R, Awad S, Kunhi M, Dzimiri N, Nguyen H, et al. FBXO32, encoding a member of the SCF complex, is mutated in dilated cardiomyopathy. Genome Biol. 2016;17:2 pubmed publisher
    ..Our results indicate that abnormal SCF activity with subsequent impairment of the autophagic flux due to a novel FBXO32 mutation is implicated in the pathogenesis of DCM. ..
  33. request reprint
    Shamseldin H, Yakulov T, Hashem A, Walz G, Alkuraya F. ANKS3 is mutated in a family with autosomal recessive laterality defect. Hum Genet. 2016;135:1233-1239 pubmed
    ..Furthermore, we describe a new mutant anks3 line that also displays laterality defect in the homozygous state. Our study suggests a role for ANKS3 in right-left axis determination in humans. ..
  34. Patel N, Shamseldin H, Sakati N, Khan A, Softa A, Al Fadhli F, et al. GZF1 Mutations Expand the Genetic Heterogeneity of Larsen Syndrome. Am J Hum Genet. 2017;100:831-836 pubmed publisher
    ..Our results suggest that GZF1 mutations cause a phenotype of severe myopia and significant articular involvement not previously described in Larsen syndrome. ..
  35. Anazi S, Shamseldin H, Alnaqeb D, Abouelhoda M, Monies D, Salih M, et al. A null mutation in TNIK defines a novel locus for intellectual disability. Hum Genet. 2016;135:773-8 pubmed publisher
    ..The phenotype we observe in human patients who lack TNIK is consistent with the previously published Tnik (-/-) phenotype in the murine model. Our data strongly implicate TNIK deficiency in the causation of ID in humans. ..
  36. Shaheen R, Anazi S, Ben Omran T, Seidahmed M, Caddle L, Palmer K, et al. Mutations in SMG9, Encoding an Essential Component of Nonsense-Mediated Decay Machinery, Cause a Multiple Congenital Anomaly Syndrome in Humans and Mice. Am J Hum Genet. 2016;98:643-52 pubmed publisher
    ..We conclude that SMG9 is required for normal human and murine development, most likely through a transcriptional regulatory role, the precise nature of which remains to be determined. ..
  37. Shaheen R, Shamseldin H, Loucks C, Seidahmed M, Ansari S, Ibrahim Khalil M, et al. Mutations in CSPP1, encoding a core centrosomal protein, cause a range of ciliopathy phenotypes in humans. Am J Hum Genet. 2014;94:73-9 pubmed publisher
    ..Our results expand the list of centrosomal proteins implicated in human ciliopathies. ..
  38. Shaheen R, Ansari S, Mardawi E, Alshammari M, Alkuraya F. Mutations in TMEM231 cause Meckel-Gruber syndrome. J Med Genet. 2013;50:160-2 pubmed publisher
    ..TMEM231 represents a novel MKS locus. The very recent identification of TMEM231 mutations in Joubert syndrome supports the growing appreciation of the overlap in the molecular pathogenesis between these two ciliopathies. ..
  39. Monies D, Abouelhoda M, AlSayed M, Alhassnan Z, Alotaibi M, Kayyali H, et al. The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes. Hum Genet. 2017;136:921-939 pubmed publisher
  40. Gueneau L, Fish R, Shamseldin H, Voisin N, Tran Mau Them F, Preiksaitiene E, et al. KIAA1109 Variants Are Associated with a Severe Disorder of Brain Development and Arthrogryposis. Am J Hum Genet. 2018;102:116-132 pubmed publisher
  41. Alkuraya F. Homozygosity mapping: one more tool in the clinical geneticist's toolbox. Genet Med. 2010;12:236-9 pubmed publisher
    ..This article is meant to highlight the clinical utility of this strategy using illustrative clinical examples from the author's own clinical genetics practice. ..
  42. Shaheen R, Han L, Faqeih E, Ewida N, Alobeid E, Phizicky E, et al. A homozygous truncating mutation in PUS3 expands the role of tRNA modification in normal cognition. Hum Genet. 2016;135:707-13 pubmed publisher
    ..Our finding adds to a growing list of intellectual disability disorders that are caused by perturbation of various tRNA modifications, which highlights the sensitivity of the brain to these highly conserved processes. ..
  43. El Hattab A, Shaheen R, Hertecant J, Galadari H, Albaqawi B, Nabil A, et al. On the phenotypic spectrum of serine biosynthesis defects. J Inherit Metab Dis. 2016;39:373-381 pubmed publisher
  44. Shamseldin H, Faqeih E, Alasmari A, Zaki M, Gleeson J, Alkuraya F. Mutations in UNC80, Encoding Part of the UNC79-UNC80-NALCN Channel Complex, Cause Autosomal-Recessive Severe Infantile Encephalopathy. Am J Hum Genet. 2016;98:210-5 pubmed publisher
    ..UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. ..
  45. Alazami A, Awad S, Coskun S, Al Hassan S, Hijazi H, Abdulwahab F, et al. TLE6 mutation causes the earliest known human embryonic lethality. Genome Biol. 2015;16:240 pubmed publisher
    ..In this first report of a human defect in a member of the subcortical maternal subcritical maternal complex, we show that the TLE6 mutation is gender-specific and leads to the earliest known human embryonic lethality phenotype. ..
  46. Shamseldin H, Tulbah M, Kurdi W, Nemer M, Alsahan N, Al Mardawi E, et al. Identification of embryonic lethal genes in humans by autozygosity mapping and exome sequencing in consanguineous families. Genome Biol. 2015;16:116 pubmed publisher
    ..Our study represents an important step towards the systematic analysis of "embryonic lethal genes" in humans. ..
  47. Sanders A, de Vrieze E, Alazami A, Alzahrani F, Malarkey E, Sorusch N, et al. KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome. Genome Biol. 2015;16:293 pubmed publisher
    ..Consistent with the mild patient phenotype, our nematode, mice and human cell data support the notion that KIAA0556 has a relatively subtle and variable cilia-related function, which we propose is related to microtubule regulation. ..
  48. Alazami A, Patel N, Shamseldin H, Anazi S, Al Dosari M, Alzahrani F, et al. Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. Cell Rep. 2015;10:148-61 pubmed publisher
    ..Overall, a likely causal mutation was identified in >73% of our cases. This study contributes to the global effort toward a full compendium of disease genes affecting brain function. ..
  49. Chelban V, Patel N, Vandrovcova J, Zanetti M, Lynch D, Ryten M, et al. Mutations in NKX6-2 Cause Progressive Spastic Ataxia and Hypomyelination. Am J Hum Genet. 2017;100:969-977 pubmed publisher
    ..Our results support a non-redundant developmental role of NKX6-2 in humans and imply that NKX6-2 mutations should be considered in the differential diagnosis of spastic ataxia and hypomyelination. ..