BACKGROUND: Angelman syndrome (AS) is a rare, genetic, neurodevelopmental disorder characterized by severe impairments in speech, cognition, and motor skills accompanied by unique behaviors, distinct facial features, and high prevalence of epilepsy and sleep problems. Despite some reports of short stature among AS patients, this feature is not included in the clinical criteria defined in 2005. We investigated growth patterns among AS patients with respect to mutation type, growth periods, family history, and endocrine abnormalities.
METHODS: Data were collected from patients\' medical files in AS National Clinic. Mutation subtypes were divided to deletion and non-deletion. Four growth periods were defined: preschool, childhood, peak height velocity, and final height.
RESULTS: The cohort included 88 individuals (46 males), with 54 (61.4%) carrying deletion subtype. A median of 3 observations per individual produced 280 data points. Final height SDS was significantly lower compared to general population (-1.23 ± 1.26, p < 0.001), and in deletion group versus non-deletion (-1.67 ± 1.3 vs. -0.65 ± 0.96, p = 0.03). Final height SDS was significantly lower compared to height SDS in preschool period (-1.32 vs. -0.47, p = 0.007). Patient\'s final height SDS was significantly lower than the parents\' (∆final-height SDS = 0.94 ± 0.99, p = 0.002). IGF1-SDS was significantly decreased compared to general population (-0.55 ± 1.61, p = 0.04), with lower values among deletion group (-0.70 ± 1.44, p = 0.01).
CONCLUSIONS: AS patients demonstrate specific growth pattern with deceleration during childhood and adolescence, resulting in significantly decreased final height compared to normal population, and even lower among deletion subgroup, which could be attributed to reduced IGF1 levels. We propose adding short stature to the clinical criteria and developing adjusted growth curves for AS population.

The vast majority of severe (Type 0) spinal muscular atrophy (SMA) cases are caused by homozygous deletions of survival motor neuron 1 (SMN1). We report a case in which the patient has two copies of SMN1 but clinically presents as Type 0 SMA. The patient is an African American male carrying a homozygous maternally inherited missense variant (c.796T>C) in a cis-oriented SMN1 duplication on one chromosome and an SMN1 deletion on the other chromosome (genotype: 2*+0). Initial extensive genetic workups including exome sequencing were negative. Deletion analysis used in the initial testing for SMA also failed to detect SMA as the patient has two copies of SMN1. Because of high clinical suspicion, SMA diagnosis was finally confirmed based on full-length SMN1 sequencing. The patient was initially treated with risdiplam and later gene therapy with onasemnogene abeparvovec at 5 months without complications. The patient\'s muscular weakness has stabilized with mild improvement. The patient is now 28 months old and remains stable and diffusely weak, with stable respiratory ventilatory support. This case highlights challenges in the diagnosis of SMA with a non-deletion genotype and provides a clinical example demonstrating that disruption of functional SMN protein polymerization through an amino acid change in the YG-box domain represents a little known but important pathogenic mechanism for SMA. Clinicians need to be mindful about the limitations of the current diagnostic approach for SMA in detecting non-deletion genotypes.

Alpha thalassemia (α-thalassemia) is an autosomal recessive disorder due to the reduction or absence of α globin chain production. Laboratory diagnosis of α-thalassemia requires molecular analysis for the confirmatory diagnosis. A screening test, comprising complete blood count, blood smear and hemoglobin quantification by high performance liquid chromatography and capillary electrophoresis, may not possibly detect all the thalassemia diseases. This review focused on the molecular techniques used to detect α-thalassemia, and the advantages and disadvantages of each technique were highlighted. Multiplex gap-polymerase chain reaction, single-tube multiplex polymerase chain reaction, multiplex ligation-dependent probe amplification, and loop-mediated isothermal amplification were used to detect common deletion of α-thalassemia. Furthermore, the reverse dot blot analysis and a single tube multiplex polymerase chain reaction could detect non-deletion mutation of the α-globin gene. Sanger sequencing is widely used to detect non-deletion mutations of α-thalassemia. Recently, next-generation sequencing was introduced in the diagnosis of both deletion and point mutations of α-thalassemia. Despite the advantages and disadvantages of different techniques, the routine method employed in the laboratory should be based on the facility, expertise, available equipment, and economic conditions.
Alfa talasemi (α-talasemi), α globin zincir üretiminin azalması ya da yokluğu nedeniyle otozomal resesif geçişli bir hastalıktır. α-talaseminin laboratuvar tanısı, doğrulayıcı tanı için moleküler analiz gerektirmektedir. Yüksek performanslı sıvı kromatografisi ve kapiler elektroforez ile tam kan sayımı, kan yayması ve hemoglobin ölçümü içeren bir tarama testi, muhtemelen tüm talasemi hastalıklarını tespit edemeyebilir. Bu derleme, α-talasemiyi saptamak için kullanılan moleküler tekniklere odaklanmış ve her tekniğin avantaj ve dezavantajları vurgulanmıştır. Ortak α-talasemi silinmesini saptamak için multipleks boşluk-polimeraz zincir reaksiyonu, tek tüplü multipleks polimeraz zincir reaksiyonu, multipleks ligasyona bağlı prob amplifikasyonu ve loop aracılı izotermal amplifikasyon kullanıldı. Ayrıca, ters nokta leke analizi ve tek tüplü multipleks polimeraz zincir reaksiyonu, α-globin geninin delesyon olmayan mutasyonunu tespit edebilir. Sanger dizilimi, α-talaseminin delesyon olmayan mutasyonlarını saptamak için yaygın olarak kullanılmaktadır. Son zamanlarda, α-talaseminin hem delesyon hem de nokta mutasyonlarının tanısında yeni nesil dizileme tanıtılmıştır. Farklı tekniklerin avantaj ve dezavantajları olmasına rağmen, laboratuvarda uygulanan rutin yöntemler tesise, uzmanlığa, mevcut ekipmana ve ekonomik koşullara dayanmalıdır.