Misdiagnosis of Tracher-Collins Syndrome Initially Attributed to Drug Teratogenicity: A Moroccan Case Report.

Background: Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial development characterized by numerous developmental anomalies that are restricted to the head and neck. Most TCS cases are inherited in an autosomal dominant manner. The diagnosis of TCS relies on clinical and radiographic findings. The four genes involved in TCS are TCOF1, POLR1D, POLR1C, and POLR1B. Case presentation: In this report, we present the case of a 7-year-old Moroccan boy who exhibited distinctive dysmorphic features, including coloboma and zygomatic bone hypoplasia. Upon genetic analysis, a mutation in the TCOF1 gene was identified, conclusively confirming the presence of Treacher Collins Syndrome. It is worthy that the correct etiological diagnosis was significantly delayed due to the initial misperception that the observed malformation syndrome was a result of drug teratogenicity. Conclusions: This case highlights the importance of seeking pharmacovigilance advice if any adverse event occurs following medication use. Furthermore, requesting a genetic consultation to establish a confirmed etiological diagnosis for any malformation syndrome can significantly reduce the protracted social and psychological suffering that patients and their families may endure.

Ankyloblepharon-ectodermal Defects-cleft Lip-palate Syndrome Due to a Novel Missense Mutation in the SAM Domain of the TP63 Gene.

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare genetic disease with an autosomal dominant transmission, characterized by several congenital anomalies. Clinical features include ectodermal defects affecting the skin, hair, teeth, nails and sweat glands, associated with typical eyelid fusion in addition to a cleft lip and/or palate. The diagnosis is based on clinical criteria and molecular genetic testing of TP63 gene, the gene related to AEC syndrome. In this context, most reported mutations induce an amino acid change in the sterile alpha motif (SAM) domain, and are predicted to disrupt protein-protein interactions. We here describe the case of a 2-year-old Moroccan girl diagnosed with AEC syndrome on the basis of clinical features. The molecular studies and bioinformatics tools revealed a novel heterozygous missense mutation c.1798G>C (p.Gly600Arg) in exon 14 of the TP63 gene, that was not found in her parents. The molecular analysis and the early diagnosis of this syndrome are important to offer appropriate genetic counseling and management to patients and their families.

Clinical and molecular report of c.1331 + 1G > A mutation of the AAAS gene in a Moroccan family with Allgrove syndrome: a case report.

BACKGROUND: Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of achalasia, alacrimia and adrenal insufficiency. It is caused by the mutations of the AAAS gene located on chromosome 12q13. The c.1331 + 1G > A mutation is one of the most common described in North Africa including Tunisia, Algeria and Libya. We report here the clinical and genetic profile of a Moroccan family with Allgrove syndrome. CASE PRESENTATION: A Moroccan sister and brother born to consanguineous parents were found, at the ages of twelve and fifteen months old respectively, to have alacrimia and isolated glucocorticoid deficiency. Later, they developed achalasia whereupon Allgrove syndrome was diagnosed clinically and confirmed by DNA sequencing which revealed a c.1331 + 1G > A mutation in the AAAS gene. CONCLUSION: This finding reinforces previous studies in demonstrating the geographic expansion of the ancestral mutation c.1331 + 1G > A in North African patients and thus enabling targeted genetic counseling. To the best of our knowledge, this is the first report of the AAAS gene mutation in Moroccan patients.

A novel TRPS1 mutation in a Moroccan family with Tricho-rhino-phalangeal syndrome type III: case report.

BACKGROUND: Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal dominant disorder characterized by craniofacial and skeletal malformations including short stature, thin scalp hair, sparse lateral eyebrows, pear-shaped nose and cone shaped epiphyses. This condition is caused by haploinsufficiency of the TRPS1 gene. Previous genotype-phenotype studies have correlated exon 6 missense mutations with TRPS type III, a severe form of type I with pronounced, facial characteristics, short stature and brachydactyly and differing from type II by the absence of exostoses and mental retardation. CASE PRESENTATION: We report the first case of a Moroccan family, a father and his three children, in which the diagnosis of type III TRPS was suspected based on severe clinical and radiological features. Molecular analysis of the TRPS1 gene revealed a novel missense mutation in exon 6, (p.Ala932Ser), located in the GATA-type DNA-binding zinc finger domain. CONCLUSION: Our observations in this kindred support the previous genotype-phenotype results suggesting that patients with more pronounced facial characteristics and more severe shortening of hands and feet are more likely to have mutation in exon 6 of TRPS1.

Acromelic frontonasal dysostosis and ZSWIM6 mutation: phenotypic spectrum and mosaicism.

Acromelic frontonasal dysostosis (AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities. A single recurrent heterozygous missense substitution in ZSWIM6, encoding a protein of unknown function, was previously shown to underlie this disorder in four unrelated cases. Here we describe four additional individuals from three families, comprising two sporadic subjects (one of whom had no limb malformation) and a mildly affected female with a severely affected son. In the latter family we demonstrate parental mosaicism through deep sequencing of DNA isolated from a variety of tissues, which each contain different levels of mutation. This has important implications for genetic counselling.

Clinical and molecular report of novel GALC mutations in Moroccan patient with Krabbe disease: case report.

BACKGROUND: Krabbe disease (KD) or globoid cell leukodystrophy is an autosomal recessive lysosomal disorder, which affects metabolic and neurologic systems. This pathology has different forms. Infantile onset is about 85% to 90% of individuals with Krabbe disease. Disorder's onset is characterized, in early childhood, by hyperirritability, psychomotor deterioration associated to episodes of fever. To date, all reported cases have been attributed to mutations in galactosylceramidase gene (GALC gene) that encodes an enzyme which degrades galactosyl-sphingolipids (galactosylceramide, psychosine), essential in myelin production. A child compounded with two new mutations in the GALC gene was detected. CASE PRESENTATION: An eleven month old male child of Moroccan origin presented to our genetic consultation with severe symptoms that included hypotonia, fever, vision loss and feeding difficulties. He was suffering from the 4th month of life. Krabbe disease was suspected. Galactocerebrosidase deficiency was confirmed by biochemical analysis. DNA sequencing revealed a novel heterozygous compound mutation in GALC gene. The child was compounded with two mutations c.860G > A; p.Cys287Tyr and c.1622G > A; p.Trp541*. CONCLUSION: These new mutations could affect GALC structure and therefore its function. The identification of these mutations and their associated phenotypes are important to predict the prognosis and to confer to families an adequate genetic counseling.

A new gene involved in X-linked mental retardation identified by analysis of an X;2 balanced translocation.

X-linked forms of mental retardation (MR) affect approximately 1 in 600 males and are likely to be highly heterogeneous. They can be categorized into syndromic (MRXS) and nonspecific (MRX) forms. In MRX forms, affected patients have no distinctive clinical or biochemical features. At least five MRX genes have been identified by positional cloning, but each accounts for only 0.5%-1.0% of MRX cases. Here we show that the gene TM4SF2 at Xp11.4 is inactivated by the X breakpoint of an X;2 balanced translocation in a patient with MR. Further investigation led to identification of TM4SF2 mutations in 2 of 33 other MRX families. RNA in situ hybridization showed that TM4SF2 is highly expressed in the central nervous system, including the cerebral cortex and hippocampus. TM4SF2 encodes a member of the tetraspanin family of proteins, which are known to contribute in molecular complexes including beta-1 integrins. We speculate that through this interaction, TM4SF2 might have a role in the control of neurite outgrowth.

Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT mutations and characterization of the mutant alleles.

The Sanfilippo syndrome type C [mucopolysaccharidosis IIIC (MPS IIIC)] is caused by mutations in the HGSNAT gene, encoding an enzyme involved in heparan sulphate degradation. We report the first molecular study on several Spanish Sanfilippo syndrome type C patients. Seven Spanish patients, one Argentinean and three Moroccan patients were analysed. All mutant alleles were identified and comprised nine distinct mutant alleles, seven of which were novel, including four missense mutations (p.A54V, p.L113P, p.G424V and p.L445P) and three splicing mutations due to two point mutations (c.633+1G>A and c.1378-1G>A) and an intronic deletion (c.821-31_821-13del). Furthermore, we found a new single nucleotide polymorphism (SNP) (c.564-98T>C). The two most frequent changes were the previously described c.372-2A>G and c.234+1G>A mutations. All five splicing mutations were experimentally confirmed by studies at the RNA level, and a minigene experiment was carried out in one case for which no fibroblasts were available. Expression assays allowed us to show the pathogenic effect of the four novel missense mutations and to confirm that the already known c.710C>A (p.P237Q) is a non-pathogenic SNP. Haplotype analyses suggested that the two mutations (c.234+1G>A and c.372-2A>G) that were present in more than one patient have a common origin, including one (c.234+1G>A) that was found in Spanish and Moroccan patients.

Prevalence of MYH-associated polyposis related to three recurrent mutations in Morocco.

BACKGROUND: MYH-associated polyposis (MAP) is an autosomal recessive inherited disease. People with MAP tend to develop multiple adenomatous colon polyps during their lifetime and have an increased risk of colorectal cancer. MAP has only recently been described and there is much to be learned about the condition. Recessively inherited mutations in the base excision repair gene MYH have recently been associated with predisposition to colorectal adenomas and cancer. The epidemiology of MYH-associated polyposis (MAP) is poorly known in populations with high levels of consanguinity like North African populations, in particular in Morocco, and the MAP carrier frequency in the general Moroccan population has never been evaluated. The present study was carried out among the Moroccan population, using molecular epidemiology methods, to estimate the prevalence of homozygote or compound heterozygote genotype conferring MAP due to three mutations reported as recurrent in MAP: c.494A>G (Y165C), c.1145G>A (G382D) and c.1186_1187insGG (p.Glu396fsX42). METHODS: To estimate the prevalence of MYH mutations in Morocco, DNA extracted from blood samples of 400 healthy Moroccans was tested for recurrent MYH mutations using real-time PCR or DNA fragment analysis. Heterozygotes profiles were confirmed by direct sequencing. We searched for the mutations c.494A>G and c.1145G>A in 400 subjects, and the mutation c.1186_1187insGG in 250 subjects. RESULTS: One subject was heterozygous for c.494A>G (1/400 or 0.25%), three others for c.1145G>A (3/400 or 0.75%) and one was heterozygous for p.Glu396fsX42 (1/250 or 0.4%). The carrier frequency of one of these three mutations in the Moroccan population was calculated to be 1.4% and the frequency of homozygous or compound heterozygote for these three recurrent mutations is 1/10 000.These figures allowed one to estimate at 3500 the number of Moroccans with high risk of developing colon cancer due only to these three recurrent mutations. CONCLUSION: This preliminary study shows that the Moroccan population is at risk for MAP. This could help to define diagnosis strategies and patient care and may also have implications for genetic counselling.

Exome sequencing revealed a novel homozygous METTL23 gene mutation leading to familial mild intellectual disability with dysmorphic features.

BACKGROUND: Genetic factors represent a considerable part of the etiologies of intellectual disability; however, the identification of causal genetic anomaly has long been complicated by the great clinical and genetic heterogeneity of this type of disease. With advances in next-generation sequencing technologies and functional studies, the identification of genes involved in intellectual development has led to more accurate diagnostics and better understanding of the underlying biological pathways. CASE REPORT: We report on the case of two Moroccan siblings presenting mild intellectual disability with minimal dysmorphic features in which whole exome sequencing analysis revealed homozygous mutation in the METTL23 gene. Mutations in this gene have been reported to cause autosomal recessive mild intellectual disability but the association with dysmorphic features remains controversial. CONCLUSION: Hereby, we highlight the similarity of the dysmorphic traits and the characteristic facial features in patients with METTL23-related intellectual disability, suggesting the consideration of a distinct clinical entity associating mild intellectual deficiency with specific facial dysmorphy for an efficient diagnosis orientation and a better phenotype-genotype correlation in intellectual disability disorders.

Consanguineous marriages in Morocco and the consequence for the incidence of autosomal recessive disorders.

Consanguineous marriage is traditionally common throughout Arab countries. This leads to an increased birth prevalence of infants with recessive disorders, congenital malformations, morbidity and mortality. The aim of this study was to evaluate the rate of consanguineous marriage in families with autosomal recessive diseases, and to compare it with the average rate of consanguinity in the Moroccan population. The study was conducted in the Department of Medical Genetics in Rabat on 176 families with autosomal recessive diseases diagnosed and confirmed by clinical, radiological, enzymatic or molecular investigations. The rate of consanguinity was also studied in 852 families who had infants with trisomy 21 confirmed by karyotyping. These families were chosen because: (i) there is no association between trisomy 21 and consanguinity, (ii) these cases are referred from different regions of Morocco and (iii) they concern all social statuses. Among 176 families with autosomal recessive disorders, consanguineous marriages comprised 59.09% of all marriages. The prevalence of consanguinity in Morocco was found to be 15.25% with a mean inbreeding coefficient of 0.0065. The differences in the rates of consanguineous marriages were highly significant when comparing the general population and couples with offspring affected by autosomal recessive conditions. These results place Morocco among the countries in the world with high rates of consanguinity. Autosomal recessive disorders are strongly associated with consanguinity. This study better defines the health risks associated with consanguinity for the development of genetic educational guidelines targeted at the public and the health sector.

Comparative clinical and transcriptomal profiles of breast cancer between French and South Mediterranean patients show minor but significative biological differences.

BACKGROUND: In Western countries, breast cancer incidence and mortality are higher than in Mediterranean countries. These differences have been ascribed to environmental factors but also to late-stage diagnostic and biological specific characteristics. PATIENTS AND METHODS: Between September 2002 and September 2005, we collected clinical data by phone counselling 180 French and Mediterranean breast cancer patients and performed microarray experiments. RESULTS: Characteristics of breast cancer in patients from Lebanon, Tunisia and Morocco were more aggressive (more SBR grade III and positive node invasion) and patients were 10 years younger at diagnosis. Sixteen differentially expressed genes such as MMP9, VEGF, PHB1, BRCA1, TFAP2C, GJA1 and TFF1 were also found. Additionally, an up-regulation of cytokeratins KRT8 and KRT18 may indicate a luminal B subtype in "South" (Lebanon, Tunisia and Morocco) tumors while "North" (France) tumors may more frequently be luminal A type. CONCLUSION: This study allowed the identification of specific clinical and transcriptomic parameters in patients from South Mediterranean countries.

Autosomal dominant anhidrotic ectodermal dysplasias at the EDARADD locus.

Anhidrotic ectodermal dysplasia (EDA) is a disorder of ectodermal differentiation characterized by sparse hair, abnormal or missing teeth, and inability to sweat. X-linked EDA is the most common form, caused by mutations in the EDA gene, which encodes ectodysplasin, a member of the tumor necrosis factor (TNF) family. Autosomal dominant and recessive forms of EDA have been also described and are accounted for by two genes. Mutations in EDAR, encoding a TNF receptor (EDAR) cause both dominant and recessive forms. In addition, mutations in a recently identified gene, EDARADD, encoding EDAR-associated death domain (EDARADD) have been shown to cause autosomal recessive EDA. Here, we report a large Moroccan family with an autosomal dominant EDA. We mapped the disease gene to chromosome 1q42.2-q43, and identified a novel missense mutation in the EDARADD gene (c.335T>G, p.Leu112Arg). Thus, the EDARADD gene accounts for both recessive and dominant EDA. EDAR is activated by its ligand, ectodysplasin, and uses EDARADD to build an intracellular complex and activate nuclear factor kappa B (NF-kB). We compared the functional consequences of the dominant (p.Leu112Arg) and recessive mutation (p.Glu142Lys), which both occurred in the death domain (DD) of EDARADD. We demonstrated that the p.Leu112Arg mutation completely abrogated NF-kB activation, whereas the p.Glu142Lys retained the ability to significantly activate the NF-kB pathway. The p.Leu112Arg mutation is probably a dominant negative form as its cotransfection impaired the wild-type EDARADD's ability to activate NF-kB. Our results confirm that NF-kB activation is impaired in EDA and support the role of EDARADD DD as a downstream effector of EDAR signaling.

[The mutation 35delG of the gene of the connexin 26 is a frequent cause of autosomal-recessive non-syndromic hearing loss in Morocco]. / La mutation 35delG du gène de la connexine 26, une cause fréquente des surdités non syndromiques autosomiques récessives au Maroc.

UNLABELLED: Mutations of the connexin 26 gene, GJB2, are the most common cause of non syndromic autosomal-recessive hearing loss. One of the GJB2 mutations, the 35delG, is recurrent in European and Mediterranean populations with allelic frequency of at least 70% in patients with hearing loss caused by GJB2 impairment. OBJECTIVES: To determine the prevalence of the 35delG mutation in non-syndromic autosomal-recessive deafness in Morocco. PATIENTS AND METHODS: We looked for the 35delG mutation among 25 non-related Moroccan children suffering from an autosomal recessive hearing loss. A screening for GJB2 mutations, and then a search for GJB6 deletions were carried out among patients who do not bear the 35delG. RESULTS: Twelve patients were homozygous for the 35delG mutation. This mutation was responsible for almost half of the hearing loss among our patients (48%). There was no other GJB2 or GJB6 mutation among 13 patients. CONCLUSION: This study underlines the advantages of a systematic search for this mutation among deaf children when environmental causes are considered irrelevant. The identification of this genetic anomaly signs the etiologic diagnosis of deafness, which allows a relevant genetic advice, and a better treatment of patients.

Clinical and molecular findings in a Moroccan family with Jervell and Lange-Nielsen syndrome: a case report.

BACKGROUND: Jervell and Lange-Nielsen syndrome (Online Mendelian Inheritance in Man 220400) is a rare autosomal recessive cardioauditory ion channel disorder that affects 1/200,000 to 1/1,000,000 children. It is characterized by congenital profound bilateral sensorineural hearing loss, a long QT interval, ventricular tachyarrhythmias, and episodes of torsade de pointes on an electrocardiogram. Cardiac symptoms arise mostly in early childhood and consist of syncopal episodes during periods of stress, exercise, or fright and are associated with a high risk of sudden cardiac death. Jervell and Lange-Nielsen syndrome is caused by homozygous or compound heterozygous mutations in KCNQ1 on 11p15.5 or KCNE1 on 1q22.1-q22.2. CASE PRESENTATION: We report the case of a 10-year-old Moroccan boy with congenital hearing loss and severely prolonged QT interval who presented with multiple episodes of syncope. His parents are first-degree cousins. We performed Sanger sequencing and identified a homozygous variant in KCNQ1 (c.1343dupC, p.Glu449Argfs*14). CONCLUSIONS: The identification of the genetic substrate in this patient confirmed the clinical diagnosis of Jervell and Lange-Nielsen syndrome and allowed us to provide him with appropriate management and genetic counseling to his family. In addition, this finding contributes to our understanding of genetic disease in the Moroccan population.

CALR gene mutational profile in myeloproliferative neoplasms with non-mutated JAK2 in Moroccan patients: A case series and germline in-frame deletion.

BACKGROUND: The discovery of somatic mutations within the gene encoding calreticulin (CALR) in 2013 represented a major milestone in the molecular diagnosis of BCR-ABL negative myeloproliferative neoplasms (MPN). In fact, exome sequencing revealed that most patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) lacking JAK2 or MPL mutations, harbor somatic insertion and/or deletion in exon 9 of CALR gene. In this study, we identified the first CALR gene mutational landscape in Moroccan patients with MPN nonmutated for the JAK2 gene. METHODS: We performed Sanger sequencing of exon 9 of CALR gene in blood samples obtained from 33 Moroccan patients with ET or PMF non-mutated for JAK2. RESULTS: Of the 33 patients analyzed, we detected eight distinct variants in 15 patients (45.4%); six indel mutations, five with type 1 recurrent 52bp deletion, four with type 2 recurrent 5bp insertion and one in frame deletion which was found to be a germline variant suggesting a very rare condition in MPN. CONCLUSION: This is the first cohort reported in CALR gene mutation analysis in Morocco. Our results were concordant with studies reported up to date and very encouraging in promoting the molecular diagnosis of myeloproliferative neoplasms in Moroccan patients. Moreover, the presence of a germline in frame deletion in a symptomatic patient should undermine the effectiveness of sizing assays without DNA sequencing in the diagnosis of CALR mutations.

Clinical and molecular findings in three Moroccan families with distal renal tubular acidosis and deafness: Report of a novel mutation of ATP6V1B1 gene.

BACKGROUND: Primary distal renal tubular acidosis (dRTA) is a rare genetic condition characterized by an impaired acid excretion by the intercalated cells in the renal collecting duct. Recessive forms of this disease are caused by mutations in tow major genes: ATP6V1B1 and ATP6V0A4. Causal mutations in ATP6V1B1 gene are classically associated with early sensorineural hearing loss, however cases of tubular acidosis with early deafness have also been described in patients with mutations in the ATP6V0A4 gene. METHODS: The phenotype and genotype of three Moroccan consanguineous families with dRTA and deafness were assessed. Molecular analysis was performed by PCR amplification and direct sequencing of exon 12 of ATP6V1B1 gene. RESULTS: A novel c.1169dupC frameshift mutation of ATP6V1B1 gene was identified in one family and the c.1155dupC North African mutation in the tow other families. DISCUSSION AND CONCLUSION: In this report, we propose first line genetic testing based on screening of these two mutations both located in exon 12 of ATP6V1B1 gene in Moroccan patients with recessive form of dRTA associated to precocious hearing loss. Molecular diagnosis of dRTA leads to appropriate treatment and prevention of renal failure in affected individuals and to provide genetic counseling for families at risk.

Homozygosity mapping of a Dyggve-Melchior-Clausen syndrome gene to chromosome 18q21.1.

Dyggve-Melchior-Clausen syndrome (DMC) is an autosomal recessive condition characterised by short trunk dwarfism, scoliosis, microcephaly, coarse facies, mental retardation, and characteristic radiological features. X rays show platyspondyly with double vertebral hump, epiphyseal dysplasia, irregular metaphyses, and a characteristic lacy appearance of the iliac crests. Electron microscopy of chondrocytes have shown widened cisternae of rough endoplasmic reticulum and biochemical analyses have shown accumulation of glucosaminoglycan in cartilage, but the pathogenesis of DMC remains unexplained. Here, we report on the homozygosity mapping of a DMC gene to chromosome 18q21.1 in seven inbred families (Zmax=9.65 at theta=0 at locus D18S1126) in the genetic interval (1.8 cM) defined by loci D18S455 and D18S363. Despite the various geographical origins of the families reported here (Morocco, Tunisia, Portugal, and Lebanon), this condition was genetically homogeneous in our series. Continuing studies will hopefully lead to the identification of the disease causing gene.

[Haemangioma of the right atrium revealed by cardiogenic shock]. / Hémangiome de l'oreillette droite révélé par un choc cardiogénique.

Intracardiac haemangioma is a very rare primary benign tumour. A 20 year old female patient, with no significant previous medical history, presented to the emergency department with cardiovascular collapse and vague abdominal pains, with no peripheral signs of cardiac failure. The electrocardiogram showed sinus rhythm with diffuse reploarisation disturbances. Chest radiography revealed cardiomegaly (cardiothoracic index of 0.67) with a right paracardial opacity. Abdominal ultrasound showed a moderate peritoneal effusion and transthoracic ultrasound showed a tumour occupying the right atrial cavity but sparing the interatrial septum. The patient underwent emergency open heart surgery for tumour resection and right atrial wall repair with autologous pericardium. Histology confirmed a haemangioma. Follow-up at one month was uneventful. The clinical, diagnostic and therapeutic features of this case are underlined.

Genetic structure of north-west Africa revealed by STR analysis.

We have analysed a large set of autosomal short tandem repeat (STR) loci in several Arabic and Berber-speaking groups from north-west Africa (ie Moroccan Arabs, northern-central and southern Moroccan Berbers, Saharawis, and Mozabites). Two levels of analysis have been devised using two sets of 12STR loci, (D3S1358, vWA, FGA, THO1, TPOX, CSF1PO, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820) and 21 (the former set plus D9S926, D11S2010, D13S767, D14S306, D18S848, D2S1328, D4S243, F13A1, and FES/FPS). For each set, data for a number of external reference populations were gathered from the literature. Several methods of analysis based on genetic distances (neighbour-joining trees, principal coordinate analysis, boundary detection), as well as AMOVA, showed that genetic differentiation among NW African populations was very low and devoid of any spatial pattern. When the NW African populations were grouped according to cultural or linguistic differences, the partition was not associated with genetic differentiation. Thus, it is likely that Arabisation was mainly a cultural process. A clear genetic difference was found between NW African populations and Iberians, which underscores the Gilbraltar Straits as a strong barrier to genetic exchange; nonetheless, some degree of gene flow into Southern Iberia may have existed. NW Africans were genetically closer to Iberians and to other Europeans than to African Americans.