{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRAB40AL encodes a mitochondrial Ras protein that was originally implicated as the causative gene for Martin–Probst syndrome (MPS), a rare X‐linked neurodevelopmental disorder characterized by sensorineural hearing loss, cognitive impairment, short stature, and distinctive craniofacial dysmorphisms. Early investigations aimed to identify the mutation underlying MPS, thereby linking RAB40AL to the clinical manifestations of this syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSubsequent studies reported a missense change, p.D59G, in RAB40AL in affected individuals, with one report describing three related males manifesting a spectrum of neurodevelopmental anomalies consistent with MPS."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " However, further investigations have demonstrated that the p.D59G variant is present at relatively high frequencies in general population cohorts, including asymptomatic males and females, thereby calling into question its pathogenic role in MPS. In one study, p.D59G was detected in about 2.47% of individuals from a Polish population, and additional findings revealed its presence in apparently healthy males with higher education, suggesting that this variant is more likely a common polymorphism than a disease‐causing mutation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOverall, the function of RAB40AL in the context of MPS has been reevaluated: while initial reports tied its p.D59G mutation to the syndrome’s neurodevelopmental phenotype, the discovery of this variant in unaffected individuals emphasizes the necessity for caution in interpreting genetic findings from next-generation sequencing. The current body of evidence supports the view that RAB40AL p.D59G is unlikely to be a pathogenic mutation responsible for MPS, underscoring the importance of comprehensive population studies in clinical genetic diagnostics.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jirair Krikor Bedoyan, Valerie M Schaibley, Weiping Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of RAB40AL function leads to Martin--Probst syndrome, a rare X-linked multisystem neurodevelopmental human disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmedgenet-2011-100575"}], "href": "https://doi.org/10.1136/jmedgenet-2011-100575"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22581972"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22581972"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "James Lee, Stacey Wong, Richard G Boles "}, {"type": "b", "children": [{"type": "t", "text": "Mutation in the X-linked RAB40AL gene (Martin-Probst syndrome) with mental retardation, sensorineural hearing loss, and anomalies of the craniofacies and genitourinary tract: a second case report."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pediatr (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00431-014-2339-x"}], "href": "https://doi.org/10.1007/s00431-014-2339-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24863632"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24863632"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Monika Ołdak, Aneta Ścieżyńska, Wojciech Młynarski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence against RAB40AL being the locus for Martin-Probst X-linked deafness-intellectual disability syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22620"}], "href": "https://doi.org/10.1002/humu.22620"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25044830"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25044830"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Monika Ołdak, Ewelina Ruszkowska, Agnieszka Pollak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A note of caution on the diagnosis of Martin-Probst syndrome by the detection of the p.D59G mutation in the RAB40AL gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pediatr (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00431-014-2452-x"}], "href": "https://doi.org/10.1007/s00431-014-2452-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25370018"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25370018"}]}]}]}