In this study, we report the experience of the only reference clinical next-generation sequencing lab in Saudi Arabia with the first 1000 families who span a wide-range of suspected Mendelian phenotypes. A total of 1019 tests were performed in the period of March 2016–December 2016 comprising 972 solo (index only), 14 duo (parents or affected siblings only), and 33 trio (index and parents). Multigene panels accounted for 672 tests, while whole exome sequencing (WES) represented the remaining 347 tests. Pathogenic or likely pathogenic variants that explain the clinical indications were identified in 34% (27% in panels and 43% in exomes), spanning 279 genes and including 165 novel variants. While recessive mutations dominated the landscape of solved cases (71% of mutations, and 97% of which are homozygous), a substantial minority (27%) were solved on the basis of dominant mutations. The highly consanguineous nature of the study population also facilitated homozygosity for many private mutations (only 32.5% of the recessive mutations are founder), as well as the first instances of recessive inheritance of previously assumed strictly dominant disorders (involving ITPR1, VAMP1, MCTP2, and TBP). Surprisingly, however, dual molecular diagnosis was only observed in 1.5% of cases. Finally, we have encountered candidate variants in 75 genes (ABHD6, ACY3, ADGRB2, ADGRG7, AGTPBP1, AHNAK2, AKAP6, ASB3, ATXN1L, C17orf62, CABP1, CCDC186, CCP110, CLSTN2, CNTN3, CNTN5, CTNNA2, CWC22, DMAP1, DMKN, DMXL1, DSCAM, DVL2, ECI1, EP400, EPB41L5, FBXL22, GAP43, GEMIN7, GIT1, GRIK4, GRSF1, GTRP1, HID1, IFNL1, KCNC4, LRRC52, MAP7D3, MCTP2, MED26, MPP7, MRPS35, MTDH, MTMR9, NECAP2, NPAT, NRAP, PAX7, PCNX, PLCH2, PLEKHF1, PTPN12, QKI, RILPL2, RIMKLA, RIMS2, RNF213, ROBO1, SEC16A, SIAH1, SIRT2, SLAIN2, SLC22A20, SMDT1, SRRT, SSTR1, ST20, SYT9, TSPAN6, UBR4, VAMP4, VPS36, WDR59, WDYHV1, and WHSC1) not previously linked to human phenotypes and these are presented to accelerate post-publication matchmaking. Two of these genes were independently mutated in more than one family with similar phenotypes, which substantiates their link to human disease (AKAP6 in intellectual disability and UBR4 in early dementia). If the novel candidate disease genes in this cohort are independently confirmed, the yield of WES will have increased to 83%, which suggests that most “negative” clinical exome tests are unsolved due to interpretation rather than technical limitations.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-017-1821-8) contains supplementary material, which is available to authorized users.

Isolated anti-HBc alone is common in Saudi patients with chronic HCV infection, and is significantly more common in those with CAH than those with cirrhosis. Therefore, a screening strategy that only tests for HBsAg and anti-HBs in these patients will miss a large number of individuals with isolated anti-HBc, who may be potentially infectious.

BACKGROUNDSaudi Arabia is a leading country in the Middle East in the field of deceased-donor liver transplantation (DDLT) and living-donor liver transplantation (LDLT). We present out experience with DDLT and LDLT at King Faisal Specialist Hospital and Research Center (KFSHRC) for the period from April 2001 to January 2007.PATIENTS AND METHODSWe performed 122 LT procedures (77 DDLTs and 45 LDLTs) in 118 patients (4 retransplants) during this period of time.RESULTSThe number of adult and pediatric procedures was 107 and 11, respectively. The overall male/female ratio was 66/52 and the median age of patients was 43 years (range, 2–63 years). In the DDLT group, the median operating time was 8 hours (range, 4–19), the median blood transfusion was 6 units (range, 0–40), and the median hospital stay was 13 days (range, 6–183). In the DDLT group, after a mean follow-up period of 760 days (range, 2–2085), the overall patient and graft survival rate was 86%. In the LDLT group, the median operating time was 11 hours (range, 7–17), the median blood transfusion was 4 units (range, 0–65), and the median hospital stay was 15 days (range, 7–127). In the LDLT group, and after a mean follow-up period of 685 days (range, 26–1540), the overall patient and graft survival rates were 90% and 80%, respectively with no significant difference in patient and graft survivals between groups. Biliary complications were significantly higher in LDLT compared to DDLT (P<0.05). Vascular complications were also significantly higher in LDLT compared DDLT (P<0.05).CONCLUSIONSBoth DDLT and LDLT are being successfully performed at KFSHRC with early experience indicating a higher rate of biliary and vascular complications in the LDLT group.

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The ULN for ALT levels in Middle Eastern populations should be lowered, including separate values for males and females. Furthermore, metabolic parameters were shown to have a significant effect on ALT levels.

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Metabolic syndrome and viral hepatitis negatively impacted our living donor pool. Expanding the donor pool requires the implementation of new strategies.

Post-transplant treatment with pegylated interferon alpha-2a and ribavirin achieved SVR in 56% of liver transplant recipients with chronic HCV genotype 4 infection. The combination was relatively safe and exhibited a low rate of treatment withdrawal.