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DSCAML1 (HGNC:14656) has emerged as a candidate gene in patients presenting with pituitary stalk interruption syndrome (PSIS), a disorder characterized by an absent or thin pituitary stalk often accompanied by an ectopic posterior pituitary (PMID:39156017). In a trio-based whole exome sequencing study of patients with ectopic posterior pituitary, DSCAML1 variants were identified among several genes of interest, prompting further investigation into its potential role in midline brain and pituitary development.
The clinical context of PSIS involves congenital hypoplasia of the anterior pituitary and associated endocrine deficiencies. In the study, affected individuals, including familial cases where a mother and son or two siblings were impacted, underwent genetic evaluation that pointed to a monogenic etiology with variable penetrance (PMID:39156017). This clustering of clinical features underscores the need for a more detailed genetic and functional workup.
From the genetic standpoint, a recurrent variant, c.2023G>T (p.Ala675Ser), was observed in a patient with PSIS, making it the representative finding for DSCAML1 in this cohort (PMID:39156017). Although the number of unrelated probands harboring this variant is limited, its recurrence in the context of PSIS provides actionable insight for further diagnostic evaluation.
Experimental evidence supporting the role of DSCAML1 comes from functional studies in zebrafish that demonstrate its necessity for proper neural circuit formation. In these models, dscaml1 deficiency impairs retinal patterning and oculomotor function (PMID:31685652), highlighting its fundamental role in neurodevelopment. Although these studies do not directly address pituitary development, they reinforce the relevance of DSCAML1 in establishing key neural structures.
Overall, the integration of genetic findings with supportive functional data yields a cautious yet informative picture: the association between DSCAML1 and PSIS is supported primarily by a limited number of genetic observations, with additional experimental data lending indirect support through the gene’s role in neural development. The modest segregation evidence, along with the isolated recurrence of the c.2023G>T (p.Ala675Ser) variant, suggests that while DSCAML1 is a plausible candidate, further studies are needed to elevate its clinical validity.
Key take‑home sentence: DSCAML1 represents a promising candidate for involvement in pituitary stalk interruption syndrome, warranting additional research to clarify its role in pituitary and midline brain development and to refine its diagnostic utility.
Gene–Disease AssociationLimitedA recurrent DSCAML1 variant was identified in approximately 1 proband with PSIS (PMID:39156017), with minimal segregation evidence. Genetic EvidenceLimitedThe c.2023G>T (p.Ala675Ser) variant observed in the trio-based study suggests a possible genetic contribution, although the data are limited to few cases (PMID:39156017). Functional EvidenceLimitedZebrafish studies indicate that dscaml1 is critical for neural circuit formation (PMID:31685652), but direct evidence linking DSCAML1 dysfunction to pituitary development is not yet established. |